TRB’s Airport Cooperative Research Program (ACRP) Synthesis 34: Subsurface Utility Engineering Information for Airports examines ways in which information on subsurface utilities is collected, maintained, and used by airports, their consultants, and the U.S. Federal Aviation Administration to help increase the effectiveness of, and enhance safety during, infrastructure development programs at airports. The report also compares the current state of technology and effective processes from other industry se...

The production of formate from CO2 is considered an attractive strategy for the long-term storage of solar renewable energy in chemical form.

Online criminals have been systematically targeting TurboTax, filing fraudulent tax returns of individuals, and diverting their tax refunds to prepaid debit, cards, stealing their personal information, and using and impairing their credit ratings. Continue reading →

IBM today announced that Faurecia, one of the world’s leading automotive suppliers, has selected IBM Cloud as a support of a major business transformation designed to accelerate digital manufacturing.

The Weather Company, an IBM Business, and PRISA Noticias, one of the world’s leading Spanish-language media groups and owner of EL PAÍS newspaper, announced today a collaboration to combine the most accurate forecasts with one of the Spanish-speaking world’s largest media groups. The Weather Company will provide in-depth weather data and forecasts, as well as tailored content across PRISA properties. In turn, PRISA Noticias will provide locally relevant articles, photos and video content within the Spanish versions of The Weather Channel app and website (weather.com). The collaboration will also enable local marketers to access advanced data-driven advertising solutions from IBM Watson Advertising (formerly The Weather Company’s ad sales business) across both companies’ properties.

IBM today announced an expansion of its mobile portfolio for enterprises as it continues to create analytics-driven and cognitive enabled enterprise iOS apps that enable organizations to accelerate digital reinvention and transform how businesses engage across industries.

IBM today announced that Westpac New Zealand, part of one of the world’s largest financial services institutions, has selected IBM’s private cloud technology to support its goal to be New Zealand’s leading digital bank. The new five year agreement is part of an extensive services and technology contract which includes Westpac migrating some of its business critical IT systems into IBM’s state-of-the-art Auckland data centre, enabling enhanced customer service.

Vodafone New Zealand, a leading telecommunications services provider, and IBM (NYSE: IBM) today announced a partnership to deliver the Digital Vodafone 2021 program in New Zealand. The vision for Digital Vodafone 2021 is to create the most engaging digital customer experience by adopting agile as a way of working, embracing new technologies and simplifying business models. The program is supported by IBM iX, one of the world’s largest digital agencies and global business design partners.

IBM (NYSE: IBM) et SAP SE (NYSE: SAP) annoncent aujourd’hui des projets communs pour accompagner leurs clients dans la modernisation de leurs systèmes et processus afin d’accélérer leur présence dans l’économie numérique. Les deux compagnies envisagent particulièrement d’innover ensemble pour créer de nouvelles solutions qui augmentent la valeur ajoutée du client en s’appuyant sur des extensions cognitives, des expériences client et utilisateur renforcées ainsi que des fonctionnalités sectorielles. Tout ceci doté de la SAP® Business Suite, du logiciel 4 SAP HANA® (SAP S/4HANA) et disponible sur site et dans le Cloud.

Dans l’objectif d’une recherche permanente d’innovation et d’anticipation, cette alliance stratégique couvre le co-développement de nouvelles offres commerciales pour l’installation et la maintenance de systèmes informatiques, monétiques et d’objets connectés. Ce domaine représente un potentiel de marché dont la croissance est estimée à 12% par an.

IBM (NYSE : IBM) lance de nouveaux programmes, services et partenariats afin d’aider les entreprises à renforcer leurs capacités à utiliser les réseaux sociaux pour se saisir de nouvelles opportunités affaires.

There's something about shooting medium format — especially in black and white. The look is unmistakeable: creamy highlights supported by lush, detailed shadows.

So it's perfectly understandable why many photographers shell out big bucks for pricey medium format gear. In fact, it's possible that some of you are at this very moment casually thinking about how cool it would be to shoot with a MF camera system.

And why not? I mean, don't you deserve it?

But a lot of the tonal qualities we often associate with medium format can be acheived on the cheap if you light your photos from the bottom end first.

Take the photo above, which was shot with a small-chip Fuji, a kit zoom and a pair of small, $25 soft boxes.
Read more »

Today's xkcd: Mouseover title: "DOWNSIDES: Adobe people may periodically email your newsroom to ask you to call it an 'Adobe® PDF document,' but they'll reverse course once they learn how sarcastically you can pronounce the registered trademark symbol." My own pet peeve, speaking of how normal humans choose to communicate, is people who send an […]

Einstein’s derivation of the Lorentz Transformation is purely theoretical. This study shows how it is related to the physical phenomenon of time dilation and length contraction. The Lorentz Transformation was first derived using the conditions of time dilation and length contraction. Later, Albert Einstein has given a different derivation of the Lorentz Transformation by using...

Without length contraction, time relativity transformation solves paradoxes and explains incongruent relativistic experiments, which allows us to build a transformation of coordinates without length contraction. For abscissa transformation, Figure 1 shows a spaceship in the frame of O1, its backend is at O1 and frontend at A1. At time zero the spaceship is stationary, from...

A discrepancy-free transformation of velocity is derived using the Time relativity transformation of coordinates because relativistic transformation of velocity creates a discrepancy. The relativistic transformation of velocity expresses the velocity u2 of an object q in frame 2 in terms of its velocity in frame 1. In frame 2 at time tq, the position of...

This is a paper produced as part of the PROP2 (Practitioner Research: Outcomes and Partnership) programme, a partnership between the Centre for Research on Families and Relationships (CRFR) at the University of Edinburgh and Iriss that was about health and social care in Scotland. This paper was written by Alan Gilmour from Glasgow City Community Health Partnership who participated in the PROP2 programme. This research aimed to gain an understanding of how training and information support contributes to positive outcomes for carers. It provided a range of information to answer specific questions such as: • Do carers feel that their needs are identified appropriately at different stages of their journey? • Does training contribute to the carer’s outcomes? • What are the barriers to carers engaging in training?

During this difficult time, as the world witnesses the relentless spread of COVID-19, the National Fire Protection Association (NFPA) has released several new resources to help stakeholders with life safety efforts. Two documents, in particular, an

Some ppl look at old pictures of themselves and go "oh look, I was so thin!". I feel like "oh, look! I still felt there was ethical employment under capitalism! XD" All told this was a really solid job that I'm really grateful that I had. I learned a lot about industry in this Province, how our energy is made (and wasted), and the scale of impact you can have in industry. Those lessons have never left me. Also, how to write an email that can stand up in court. Thanks, EnergyWise. 

Ali Nouri, a 2006 Princeton graduate alumnus and president of the Federation of American Scientists, is the latest guest on the "We Roar" podcast.

Princeton researchers have been awarded a National Science Foundation RAPID grant to study how anxiety about COVID-19 influences how we learn and share information about the pandemic.

A graph of the spread of fake news -- conspiracy theories, propaganda and disinformation -- would likely run parallel to that of the coronavirus itself.

El Camino Real Charter High School has won this year's state Academic Decathlon, narrowly edging out its perennial rival, Granada Hills Charter High School.

Scientists are using the coronavirus to study the contagion of misinformation

A recent IAEA report on Iran’s nuclear program was portrayed by most Western mainstream media and politicians as new proof Iran is close to building nuclear weapons. The US Senate passed sanctions on Iran targeting its central bank in response.

However, the report does not say what the mainstream media and politicians claim. It has been much more guarded and much of it is about the state of Iran’s program up to 2003. After that period, the report is much more uncertain. Furthermore, many experts contend that the speculations (not definitive proof) that are in the report are misguided, too, leaning on unreliable sources, for example.

This update to the page on Iran has more information about this. Although the page is long, look for the new section about half way down under the heading of Regurgitating old stories as new information to justify sanctions?

Read full article: Iran

The task of introducing a vaccine for the coronavirus faces an uphill struggle in Africa, where a flood of online misinformation is feeding on mistrust of Western medical research.

• Facebook is taking a harder line on misinformation related to coronavirus than it has on other health topics in the past.
• This decision may increase the pressure on the company to act more decisively against other forms of harmful falsehoods that spread on its social networks.
• Facebook is banning events that promote flouting lockdown protests, and is removing the conspiracy theory video "Plandemic."
• But false claims that vaccines are dangerous still proliferate on Facebook — even though they contribute to the deaths of children.

Amid the pandemic, Facebook is taking a harder line on misinformation than it has in the past. That decision may come back to haunt it.

As coronavirus has wreaked havoc across the globe, forcing lockdowns and disrupting economies, false information and hoaxes have spread like wildfire on social media. Miracle cures, intentional disinformation about government policies, and wild claims that Bill Gates orchestrated the entire health crisis abound.

In the past, Facebook has been heavily criticised for failing to take action to stop its platform being used to facilitate the spread of misinformation. To be sure, coronavirus falsehoods are still easily found on Facebook — but the company has taken more decisive action than in previous years:

• For starters, Facebook is now displaying warning messages to people who have shared false information about COVID-19. They're imperfect — Stat reported that they may be too vague in their wording to have a major impact — but it's a step further than Facebook has taken on misinformation in the past.
• The company is also taking down event pages for events that reject mainstream science on coronavirus by calling on people to flout lockdown rules.
• And it is banning "Plandemic," a conspiratorial video about coronavirus that has been going viral on social media and contains numerous falsehoods.

But Facebook's actions to combat COVID-19 misinformation may backfire — in the sense that it has the potential to dramatically increase pressure on the company to take stronger action against other forms of misinformation.

The company has long struggled with how to handle fake news and hoaxes; historically, its approach is not to delete them, but to try to artificially stifle their reach via algorithmic tweaks. Despite this, pseudoscience, anti-government conspiracy theories, and other falsehoods still abound on the social network.

Facebook has now demonstrated that it is willing to take more decisive action on misinformation, when the stakes are high enough. Its critics may subsequently ask why it is so reticent to combat the issue when it causes harm in other areas — particularly around other medical misinformation.

One expected defence for Facebook? That it is focused on taking down content that causes "imminent harm," and while COVID-19 misinformation falls into that category, lots of other sorts of falsehoods don't.

However, using "imminence" as the barometer of acceptability is dubious: Vaccine denialism directly results in the deaths of babies and children. That this harm isn't "imminent" doesn't make it any less dangerous — but, for now, such material is freely posted on Facebook.

Far-right conspiracy theories like Pizzagate, and more recent, Qanon, have also spread on Facebook — stoking baseless fears of shadowy cabals secretly controlling the government. These theories don't intrinsically incite harm, but have been linked to multiple acts of violence, from a Pizzagate believer firing his weapon in a pizza parlour to the Qanon-linked killing of a Gambino crime boss. (Earlier this week, Facebook did take down some popular QAnon pages — but for breaking its rules on fake profiles, rather than disinformation.)

And Facebook is still full of groups rallying against 5G technology, making evidence-free claims about its health effects (and now, sometimes linking it to coronavirus in a messy web). These posts exist on a continuum, with believers at the extreme end attempting to burn down radio towers and assault technicians; Facebook does take down such incitements to violence, but the more general fearmongering that can act as a gateway to more extreme action remains.

This week, Facebook announced the first 20 members of its Oversight Board — a "Supreme Court"-style entity that will review reports from users make rulings as to what objectionable content is and isn't allowed on Facebook and Instagram, with — in theory — the power to overrule the company. It remains to be seen whether its decisions may affect the company's approach for misinformation, and it still needs to appoint the rest of its members and get up and running.

For now, limits remain in place as to what Facebook will countenance in its fight against coronavirus-specific misinformation.

CEO Mark Zuckerberg said the company would immediately take down posts advertising dangerous false cures to COVID-19, like drinking bleach. It is "obviously going to create imminent harm," he said in March. "That is just in a completely different class of content than the back-and-forth accusations a candidate might make in an election."

But in April, President Donald Trump suggested that people might try injecting a "disinfectant" as a cure, which both has the potential to be extremely harmful, and will not cure coronavirus.

Facebook is not taking down video of his comments.

Do you work at Facebook? Contact Business Insider reporter Rob Price via encrypted messaging app Signal (+1 650-636-6268), encrypted email (robaeprice@protonmail.com), standard email (rprice@businessinsider.com), Telegram/Wickr/WeChat (robaeprice), or Twitter DM (@robaeprice). We can keep sources anonymous. Use a non-work device to reach out. PR pitches by standard email only, please.

SEE ALSO: Facebook announced the first 20 members of its oversight board that will decide what controversial content is allowed on Facebook and Instagram

Join the conversation about this story »

NOW WATCH: A cleaning expert reveals her 3-step method for cleaning your entire home quickly

• The storied investment bank is seeing leadership shakeups under CEO David Solomon and a slew of partner departures. 
• Goldman has been moving away from high-risk businesses like trading and is making pushes into more stable areas like consumer lending, wealth management, and transaction banking. 
• There have been big cultural changes, too. Solomon is looking to create a more transparent workplace, while new tech execs are taking cues from Silicon Valley heavy-hitters. 
• At Business Insider, we are closely tracking the latest developments at Goldman. You can read all of our Goldman coverage on BI Prime.

Storied Wall Street bank Goldman Sachs is going through some massive changes under CEO David Solomon.

It's taken big steps involving transparency and inclusion to change up its culture. It has seen a slew of partner departures — many in the securities division. And it's making big pushes into businesses like wealth management and transaction banking.  

The latest people moves

• Goldman Sachs just hired Kurt Hoffman, an expert in distressed situations and bankruptcy, to join a trading unit known for some of the bank's most lucrative deals
• Goldman Sachs' top tech exec explains how a fresh slew of senior hires are transforming the bank's approach to building products
• Read the full memo Goldman Sachs just sent naming 4 execs to lead its private-equity investments across the merchant-banking division

Culture and talent

• Read the full memo Goldman Sachs just sent to staff announcing its new head of regulatory affairs. The former White House counsel will be tasked with helping clean up the bank's 1MDB drama.
• Goldman Sachs just hired 2 senior recruiting execs focused on luring top talent from other firms —and it's a huge departure from the firm's traditional promote-from-within mentality
• Read the full memo David Solomon just sent to 38,000 Goldman Sachs employees explaining why he's moving his management team out of stuffy offices and into open seating
• Goldman Sachs CEO David Solomon and his management team are ditching their stuffy offices and moving to an open floor plan closer to the people so they can feel the buzz of New York headquarters
• Goldman Sachs just unveiled a new gender pronouns initiative as part of a broader inclusion push at the Wall Street firm
• Read the memo Goldman Sachs just sent to its employees unveiling a new pronouns initiative

Coronavirus response

• Inside a 38,000-person remote work rollout at Goldman Sachs: sleepless nights, assembly lines, and an Amazon-like hub on a Manhattan trading floor
• How a massive New York hospital secured 130,000 N95 masks from China with help from a senior partner at Goldman Sachs, private jets, and a call to Warren Buffett
• Goldman Sachs CEO David Solomon just sent a firm-wide voicemail about the coronavirus crisis. Here's what he told employees.
• Goldman Sachs and Bank of America just updated their WFH policies — again. Here's what they're telling employees about the latest steps aimed at combating the spread of coronavirus.
• Read the full memo Goldman Sachs top brass just sent detailing the firm's coronavirus contingency plans, including separating employees into 'blue' and 'white' teams to alternate working from the office and home

Consumer push, transaction banking, wealth management

• Goldman Sachs just announced its first partnership for transaction banking as it looks to build a new $1 billion business moving money around the world
• Goldman Sachs is sending much less mail to potential Marcus customers. A senior exec lays out the reason why.
• A Goldman Sachs exec explains why the bank isn't sweating concerns over the Apple Card's profitability
• A Wall Street firm crunched the numbers around how much Apple will make from its new credit card with Goldman Sachs
• Here's why Goldman Sachs just did its biggest deal in nearly 20 years as part of a pivot to less wealthy clients
• Goldman Sachs execs are opening up about their plans for Marcus, and they think it can do to banking what iTunes did to the music industry
• Goldman Sachs' partnership with Apple could move it a step closer to being 'a bank branch in your pocket'
• Human resources is the next battleground for Wall Street wealth advisers as Morgan Stanley and Goldman Sachs jockey over new turf
• Goldman Sachs has a novel method for predicting the next economic slump, and it's at the heart of its hot new business

Technology

• JPMorgan and Goldman Sachs are finally beginning to embrace fintech startups. Here's how they test the waters before committing to working with them.
• We talked to the execs behind Bloomberg's new data partnership with Goldman Sachs. Here's why they think it's a sign of Wall Street's future.
• Goldman Sachs is putting its own Marquee app on Amazon's cloud in a pitch to lure more fintech developers
• Goldman Sachs is embracing open-source code and its chief data officer says it's part of a "new world" of software
• Read the memo the new Goldman tech chief sent to the firm's 9,000-plus engineers where he urges them to ditch presentations in favor of Amazon's famous narratives
• A new Goldman Sachs tech exec hired from Amazon is taking a page from the Jeff Bezos playbook by urging engineers to ditch PowerPoint and write memos
• Goldman Sachs' new CTO shares his strategy for attracting outside developers to work more closely with the bank, giving a glimpse into the future of how Wall Street will work
• A Verizon executive is joining Goldman Sachs as chief technology officer as the Wall Street bank reshuffles its ranks
• Marty Chavez is retiring from Goldman Sachs. We chatted with him about the bank's tech transformation, why now is the right time for him to step down, and what he's planning next.
• Goldman Sachs tech guru Marty Chavez is retiring from the bank
• Goldman Sachs' CEO just warned that the bank's big tech bets might not pay off as quickly as people hope
• Goldman Sachs is scrapping a homegrown email app it once touted — and it's a sign the bank is moving away from building tech in house
• Goldman Sachs is exploring plans to create a Netflix for data, and it marks a new frontier for Wall Street
• Goldman Sachs' internal idea factory hatched a plan for the Google of Wall Street, and it's now looking for the next big thing to disrupt the bank
• Goldman Sachs' big bet on the future of Wall Street had a rocky start. Here's the inside story of the bank's struggle to grow its next business and an exclusive look at its plans

Trading

• Bank of America is shaking up its global markets division and poached a Goldman Sachs exec to fill a key new role
• Goldman Sachs' massive quant business now rivals AQR and Two Sigma. We talked to the bank's top quant about asset growth, finding data sources, and why critics of computerized trading are wrong.
• Goldman Sachs' CEO tells us the bank is winning over quant clients. That helped it outpace rivals like JPMorgan last quarter.
• Goldman Sachs is cutting about 5% of sales and trading staff after senior equities leaders delivered a tough town-hall talk
• Goldman Sachs is moving away from a tool championed by its former CFO as it pushes its traders to see clients where they once saw quick wins
• Goldman Sachs is shuffling its top stock trading executives as the business tries to claw back market share from Morgan Stanley and JPMorgan
• Goldman Sachs's bond trading unit is still trying to find its way — and it represents a key challenge for new CEO David Solomon

Alternatives

• Read the full memo Goldman Sachs just sent naming 4 execs to lead its private-equity investments across the merchant-banking division
• Goldman Sachs is making targeted hires for a 'storefront' for alternative investments that's modeled after firms like KKR and Blackstone
• Goldman Sachs' push into private equity is ruffling feathers at Blackstone — and it might be a sign of big client skirmishes to come
• Goldman Sachs execs are jockeying for control of the firm's lucrative private investing units after a plan to merge it — and the stakes couldn't be higher
• Meet the Goldman Sachs execs tasked with building the firms' new Blackstone-esque private-investing unit — and pumping up the bank's flagging stock price
• 'It's good to be Rich': Meet the Goldman Sachs banker who has built a private investing empire that goes head-to-head with Blackstone — and you've probably never heard of him
• Goldman Sachs is considering a shakeup of its alternative investing units as part of a plan to simplify the bank's strategy

Deals

• Goldman Sachs is assembling a team of senior bankers focused on middle-market private equity. Here are the key hires and the playbook they'll use to land new clients.
• Goldman Sachs unloaded some of its WeWork shares before its investment bankers pitched investors on what it once considered a $60 billion-plus IPO
• Goldman Sachs just revealed it sold part of its Uber stake to SoftBank and it helped boost a $4.5 billion business
• A senior Goldman Sachs fintech banker was about to join JPMorgan — but then got lured back —and it's another sign of the fierce battle for M&A talent
• Goldman just promoted a star tech banker close to Tesla and Microsoft to co-head one of its most profitable businesses, as incoming CEO Solomon makes his mark
• Goldman Sachs just announced a shakeup of its leadership — and it signals the rise of bankers over traders
• A tug-of-war between Goldman Sachs and JPMorgan over a top banker highlights Wall Street's $1 trillion battleground

Investor day 2020

• Inside Goldman Sachs' first investor day, where avocado toast and crab apples were served with tech talk, 3-year plans, and a surprising trading mea culpa
• Goldman Sachs just revealed a new wealth brand at its first-ever investor day. It shows how the bank is trying to reshape its strategy — and image.
• Goldman Sachs just unveiled hundreds of slides laying out the future of the company. Here are the 10 crucial slides that show how it plans to transform into a bank for everyone.
• Goldman Sachs is rethinking how it makes private-equity bets with its own money – and one analyst thinks that shift will be a big driver of its stock price

Careers 

• Goldman Sachs is now hiring high-school graduates for roles in Salt Lake City, one of the company's 'high value' locations
• Goldman Sachs has lost at least 54 partners since David Solomon became CEO. We're keeping a running list — and compiling details from insiders about how the exits are being celebrated.
• Read the full memo Goldman Sachs' top brass just sent to staff announcing 2 heads of the bank's private-investing arm are out as it's gearing up to raise billions
• 2 coheads of Goldman Sachs' private-investing business are retiring, in a blow to David Solomon's fundraising plans
• A Goldman Sachs partner who just resigned is leaving behind a job overseeing $2 billion for a London VC with a leading stake in neobank Revolut
• Read the memo announcing the departure of Adam Korn, the Goldman Sachs exec who was 'instrumental in building and championing' innovations like the bank's Marquee platform
• Another Goldman Sachs partner is out. HR chief Dane Holmes is the latest key player to leave the Wall Street bank in a matter of days.
• Goldman Sachs is offering buyouts to encourage partners to leave as CEO David Solomon works to shrink one of the most elite clubs on Wall Street
• Goldman Sachs is making renewable energy a big priority based on its hiring strategy. It's a sign that its ideas incubator is working.
• The David Solomon era at Goldman Sachs kicked off with 43 words Lloyd Blankfein would never say
• Goldman Sachs CEO David Solomon shares his best leadership advice
• Goldman Sachs is shaking up the way it stocks one of the most elite clubs on Wall Street — and it shows how banks are back to making money again
• Goldman Sachs' 1MDB problems are eating into employee morale, and insiders worry the firm will use its legal woes as an excuse to scrimp on bonuses
• Goldman Sachs is about to move dozens of jobs out of pricey New York to Utah as Wall Street turns to cheaper cities

Join the conversation about this story »

NOW WATCH: A cleaning expert reveals her 3-step method for cleaning your entire home quickly

You can listen to this version of the 'world's most joyous song' here.

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

Marilyn Goudreault
Jan 1, 2009; 8:157-171
Research

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.

Invitation Only Research Event

Event participants

13 March 2014 , Volume 90, Number 2

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles

Mohamad Navab
Sep 1, 2000; 41:1481-1494
Articles

JL Dixon
Feb 1, 1993; 34:167-179
Reviews

Jason M. Ridlon
Feb 1, 2006; 47:241-259
Reviews

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

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.

Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates

Event participants

Christophe Bellmann, Associate Fellow, Hoffmann Centre for Sustainable Resource Economy, Chatham House

Carolyn Deere Birkbeck, Associate Fellow, Global Economy and Finance Department and Hoffmann Centre for Sustainable Resource Economy, Chatham House

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (^–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­