The redox-coupled proton-channel opening in cytochrome c oxidase

Cytochrome c oxidase (CcO), a redox-coupled proton pump, catalyzes the reduction of molecular oxygen to water, thereby establishing the transmembrane proton gradient that fuels ATP synthesis. CcO employs two channels for proton uptake, the D- and the K-channel. In contrast to the D-channel, the K-channel does not constitute a continuous pathway of H-bonds for proton conduction and is only active in the reductive phase rendering its proton transport mechanism enigmatic. Theoretical studies have suggested selective hydration changes within the K-channel to become activated and being essential for vectorial proton transport. Here, we unravel a previously unidentified mechanism for transient proton channel activation by combining computational studies with site-directed nano-environmental probing of protonation, structural changes, and water dynamics. We show that electrostatic changes at the binuclear center lead to long-range conformational changes propagating to the K-channel entrance as evidenced by time-resolved fluorescence depolarization experiments and molecular dynamics (MD) simulations. These redox-induced long-range structural rearrangements affect the H-bond network at the K-channel's protein surface as shown by pKa-shift analysis of a local probe in experiment and simulation. Concomitantly, selective channel hydration at the K-channel entrance was revealed by dipolar relaxation studies to be associated with channel opening. We propose that instead of a singular change, it is the intricate interplay of these individual redox-triggered changes in the cause–effect relationship that defines the mechanism for transient proton conduction of the K-channel

The Grizzly, February 14, 2008

Writer\u27s Strike May See a Silver Lining • Ellison Unveils Art Exhibit in Berman • Relief for Students? College Endowments Skyrocket • Ursinus Designs New Certificate for International Studies • Is Everybody Really Doing It? The Indictment of the Greek Community at Ursinus College Surprises Many • Ursinus Community Shares its Dirty Little Secrets • Focus the Nation and Environmentalism: No Longer Just for Hippies • UC Study Abroad Helpful Hints • Opinions: Lessons from Super Tuesday; Does The Times Need Bill Kristol?; Lessons from the Hormuz Strait • Ursinus Wrestlers Clinch Dual Meet • UC Indoor Track Teams Make Big Moves, Heat Up Competitionhttps://digitalcommons.ursinus.edu/grizzlynews/1755/thumbnail.jp

The Grizzly, February 28, 2008

Tragedy Strikes at Northern Illinois University • Safety at Ursinus College in Light of the NIU Massacre • Anti-HIV Gel Fails Clinical Trial, Opens Doors • Investigating the Seven-Day Itch • Great Wall vs. China Jade: Local Chinese Dining • Third Annual CoSA Celebration Hits Ursinus in April • Review of SPINTfest at UC • Opinions: NME Scandal: An Outsider\u27s Take; Why Kosovo\u27s Independence Matters • Strong Champs for UC Swim • Gymnastics Prepares for Nationalshttps://digitalcommons.ursinus.edu/grizzlynews/1757/thumbnail.jp

The Grizzly, April 10, 2008

Baby Dies from Lack of Medical Attention, Parents Charged • Relay is Here! • Dancing at Lughnasa Opens at UC • Yes, It\u27s a Positions Article • Airband\u27s 25th Raises $3100 for the Laurel House • Senior\u27s Helpful Hints for Class Registration • Glancing at the Future of Collegeville • Men\u27s Golf Swings into Season • Track Teams Win Goucher Classichttps://digitalcommons.ursinus.edu/grizzlynews/1761/thumbnail.jp

Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium.

The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish. Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain-of-function could not recover PE formation in the absence of Bmp signaling. Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.Nadia Mercader was funded by the Spanish Ministry of Economy and Competitiveness through grant BFU2014-56970-P (Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016. Programa Estatal de I+D+i Orientada a los Retos de la Sociedad Retos Investigación: Proyectos I+D +i 2016, del Ministerio de Economía competitividad e Industria), and cofunding by Fondo Europeo de Desarrollo Regional (FEDER). Nadia Mercader is also supported by the European Industrial Doctorate Program EID 722427. Nadia Mercader and Julien Vermot are supported by the Swiss National Science Foundation grant ANR-SNF 310030L_182575. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 708312 (MP) and from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme: GA Nº682938. Laura Andrés-Delgado was funded (2014-16) through the postdoctoral fellowship Ayudas Postdoctorales 2013. José Luis de la Pompa was supported by grants SAF2016-78370-R, CB16/11/00399 (CIBER CV) and RD16/0011/0021 (TERCEL) from the Spanish Ministry of Science and Innovation. The CNIC is supported by the Ministry of Science and Innovation and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

García, Xavier (ed.) (2015). Joan Oliver-Joaquim Molas: Diàleg epistolar il·lustrat (1959-1982). Lleida: Pagès Editors, pp. 186

<p><i>Objectives</i>: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. <i>Methods</i>: We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. <i>Results</i>: In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. <i>Conclusions</i>: The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.</p

The Grizzly, April 3, 2008

Crude Awakening: Ways to Beat Surging Gas Pump Prices • Airband Turns 25 • Herpes Hindrance: Part Two • Literary Food Fest • Lou\u27s Too: The Charming Steak Shop • Fully Loaded EV Performance Attracts Full House • Faculty Spotlight: Dr. Goldsmith • Opinions: Fed Bailout? Fed, Butt Out!; Olympic Controversy • Men\u27s Lax Defeats McDaniel • Women\u27s Lax Shames McDanielhttps://digitalcommons.ursinus.edu/grizzlynews/1760/thumbnail.jp

The Grizzly, March 6, 2008

President Strassburger\u27s Message to Campus About New Member Education • Students Flock to Ursinus Job and Internship Fair • SIFE: An Organization Suited for All Ursinus Majors • The Real Inspector Hound: Stoppard Performed at UC • Local Venues Offer Break Options • Ursinus Fraternities Participate in Community Service • Da Vinci\u27s Pub: Are You a Renaissance Man or Woman? • Opinions: Anthony\u27s Keys to Making Friends; Academic Integrity for the Rest of Us; Rethinking the Second Amendment: What Does it Protect? • Football Coach Kevin Barger Moving On • Congrats to the 2008 Centennial Conference Champs! • Baseball and Softball Aim to Hit it Out of the Park • Two Head to Wrestling Nationalshttps://digitalcommons.ursinus.edu/grizzlynews/1758/thumbnail.jp