Defying the tyranny of the signature dish can be risky, but sometimes it reveals a restaurant's hidden talents.
Dining out involves grappling with countless variables before you even order. Is your reservation at a civilized hour? Do you have a desirable table next to attractive patrons who aren't talking about finance or constantly photographing their food? Are you located in what you consider to be a prime location of the restaurant, preferably in view of the main entrance (but not so close that you get a chill, mind)?
Then the menu arrives, with its list of small plates, and a hovering waiter eager to explain it. This is all unwelcome, of course, but there is one thing everybody wants to know: What is the chef's signature dish? You probably know this ahead of time. The Times and New York magazine and the rest of the reviews conveniently put it in a box, with equally pressing information like the address, phone number, and whether or not they take American Express.
Every so often, there is one item on a menu that's so out of place that it catches your eye: What is that doing there?
Some restaurants signal an important dish by adorning it with hard-to-miss graphic flourishes. On Rotisserie Georgette's lunch menu, the highly recommended poulet frites is surrounded by a tall ellipsis. At Peter Luger, if you even bother to look at a menu, you'll find a large box that says Steak for Two, Steak for Three, and so on. Traditionally, most menus have had their own internal logic—you progress from light to heavy, from fish to fowl and on to beef. There are rarely surprises. But every so often, there is one item on a menu that's so out of place that it catches your eye: What is that doing there?
It's either a woeful miscalculation or something so incongruous it must be truly inspired. Not the three-pound lobster at a steak restaurant, or a token gluten-free choice. No, this is a dish with some thought behind it, but one that still seems out of place. Like a comic actor playing Hamlet, it's either a poor gimmick or truly visionary. Think of it as ordering Siberia.
This thought occurred to me when numerous friends mentioned that the burger at Lure, the Soho seafood restaurant, was surprisingly good. If you go to a restaurant that serves sushi, chances are you're not going to progress to the burger. But like those people who go to a concert to see the opening act, there is a knowing circle of aficionados that goes to Lure just for the beef.
The dish that's always surprised me most is the duck at Le Bernardin. The only meat on a menu entirely devoted to seafood, it's under the mercurial menu category "Upon Request," as if it should be ordered in a whisper. Just what happens when you make this request? Does the waiter raise an eyebrow? Are you discretely escorted from the dining room? Does Eric Ripert come out of the kitchen and explain the premise of the entire restaurant?
So I went to Le Bernardin with the perverse intention of not even ordering fish. This struck me as downright devious—in the four-star dining sense, as incongruous as buying a painting by Bob Dylan. The no-fish plan was quickly dashed when the kitchen brought out its wonderful salmon rillette to start. Then I enjoyed a finely sliced artichoke with a light vegetable risotto in lemon broth. Delightful.
One of the conditions of ordering Siberia is that you don't know what you're getting into—it's necessarily unexpected..
The main course was crispy duck breast, slightly salted, quite rare, garnished with snow peas and finished with a sour cherry sauce. Was it good? Of course it was good; everything at Le Bernardin is beautifully executed. I drank red wine. I've never had red wine at Le Bernardin before. Then I thought a moment. Eric Ripert, and his chefs, are clearly inspired by fish—that's what drives them, what animates their cooking. That's what they dream about, why the restaurant exists, and, ultimately, why it excels. My meal was lovely, but it wasn't transporting in the way other meals I've had there were. Le Bernardin makes it seem like they've invented every fish they serve—each preparation feels like the first time you're truly tasting something. This duck experience felt more earthbound. And the fault was certainly not theirs—I ordered the meal. They didn't misrepresent themselves; I did that myself.
It doesn't have to be that way. At Le Grand Vefour, the two-star Michelin restaurant on the Palais Royal in Paris, the historic room is remarkably elegant. Colette ate there, as did Fragonard. There's a dish that neither would recognize at the bottom of chef Guy Martin's otherwise reassuring menu: The last of the desserts is an artichoke tart. It's a compelling suggestion. It turns out to be neither sweet nor savory, a thin layer of crème brulee combined with artichokes, and covered with candied vegetables. It's masterful.
One of the conditions of ordering Siberia is that you don't know what you're getting into—it's necessarily unexpected. There's a backstory you're eager to learn, like when a mysterious guest shows up at a party. The Monte Carlo, in my hometown Minneapolis, serves steak, chops, and fried chicken in a classic midcentury room. They also offer beef liver. I asked once what that was doing there, and the owner said he tried to take it off the menu, but a small, vocal minority came in to order just that, and they would be damned if it was going to go away.
One suspects that's what chicken hash is still doing at the '21' Club—that it got grandfathered in, and that there are devotees who insisted on its presence. And that's the beauty of ordering Siberia. It's a reminder that traditions can't be predicted, and that every unexpected dish was new once, hoping to become a standby with its own devoted following.


text:
Progressive Corporation
Progressive Party (United States, 1912)
Software (development cooperation)
Software (album)
Software (disambiguation)
Progressive may refer to:
Progressive (album), a demo by the band Haggard
"Progressive" (song), Kalafina's sixth single
Progressive music (disambiguation), a number of similarly-named musical genres
Progressive rock (radio format), a radio station programming format
The Progressive, an American left-wing magazine
Progressive Era, a period of reform in the United States (ca. 1890–1930)
Progressive Party (disambiguation), any of several political parties
Progressive realism, an American foreign policy paradigm focused on producing measurable results in pursuit of widely supported goals
Progressive tax, a type of tax rate structure
Progressivism, a political philosophy
Progressivism in the United States, the political philosophy in the American context
Congressional Progressive Caucus, members within the Democratic Party in the United States Congress dedicated to the advancement of progressive issues and positions
Progressive Corporation, a U.S. insurance company
This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Progressive
The Progressive Corporation is one of the largest providers of car insurance in the United States. The company also insures motorcycles, boats, RVs and commercial vehicles, and provides home insurance through select companies. Progressive has expanded internationally as well, offering car insurance in Australia. The company was co-founded in 1937 by Jack Green and Joseph M. Lewis, and is headquartered in Mayfield Village, Ohio.
The company operates in three segments: Personal Lines, Commercial Auto, and Other-indemnity. The Personal Lines segment writes insurance for private passenger automobiles, motorcycles, boats, and recreational vehicles through both an independent agency channel and a direct channel. The Commercial Auto segment writes primary liability and physical damage insurance for automobiles and trucks owned by businesses primarily through the independent agency channel. The Other-indemnity segment provides professional liability insurance to community banks, principally directors, and officers liability insurance. It also provides insurance-related services, primarily providing policy issuance and claims adjusting services in 25 states for Commercial Auto Insurance Procedures/Plans. In 2011, the company was ranked 164 in the Fortune 500.
This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Progressive_Corporation
The Progressive Party of 1912 was an American political party. It was formed by former President Theodore Roosevelt, after a split in the Republican Party between him and President William Howard Taft.
The party also became known as the Bull Moose Party after journalists quoted Roosevelt saying "I feel like a bull moose" shortly after the new party was formed.
Birth of a new party
Roosevelt left office in 1909. He had selected Taft, his Secretary of War, to succeed him as presidential candidate, and Taft easily won the 1908 presidential election. Roosevelt became disappointed by Taft's increasingly conservative policies. Taft upset Roosevelt when he used the Sherman Anti-Trust Act to break up U.S. Steel. During his own presidency, Roosevelt had approved J.P. Morgan-owned U.S. Steel as a "good" trust. They became openly hostile, and Roosevelt decided to seek the presidency.
Roosevelt entered the campaign late, as Taft was already being challenged by progressive leader Senator Robert La Follette of Wisconsin.
This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Progressive_Party_(United_States,_1912)
Hardware (development cooperation)
Orgware (developmental cooperation)
Hoekman, B. (2002). "Strengthening the Global Trade Architecture for Development". The World Bank and CEPR. CiteSeerX: 10.1.1.17.6157.
Dobrov, D.M. (1979). "The strategy for organized technology in the light of hard-, soft-, and org-ware interaction". Long Range Planning 12 (4): 79–90.
This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Software_(development_cooperation)
Software is Grace Slick's 1984 album released by RCA Records. This album was recorded after she had re-joined Jefferson Starship. After working on this album, Peter Wolf would go on to contribute to Jefferson Starship's 1984 album, Nuclear Furniture. A music video was made for the single "All the Machines". "Software" is Grace Slick's fourth and final solo album.
Software has been described as Slick's attempt to assimilate with the techno-pop artists of the period. Guitar use is largely replaced by synthesizers and electric drums. Slick's trademark wailing vocals and improvising is replaced by more short short, precise bursts. The album failed to chart.
All lyrics by Grace Slick / music by Peter Wolf except where noted
"All the Machines (edited)" – 3:34 b/w "All the Machines" – 4:47 (1984)
"Through the Window" b/w "Habits" (1984)
Grace Slick – lead vocals, background vocals
Peter Wolf – keyboards, linn programming, synth bass
Peter Maunu – guitars on all tracks except "Rearrange My Face"
This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Software_(album)
Software usually refers to instructions for computer hardware to execute.
Software may also refer to:
IEEE Software, a magazine
Software (development cooperation), used in development cooperation jargon to indicate the human aspect in technology transfer
Software (novel), part of the Ware Tetralogy, a 1982 cyber-punk novel by Rudy Rucker
Software (band), a German electronic duo active between 1984 and 2000
Software, Etc., a predecessor of the video game retailer GameStop
This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Software_(disambiguation)
softwaresoftwarejobs.com
pcprivacysoftware.com
punjabisoftware.com
softwareprogressive.com
americasoftwarejobs.com
acupuncturesoftware.com
softwareactualite.com
bahamassoftware.com
softwarefreeview.com
osakasoftware.com
softwarehousewife.com
islandprogressive.com
coalminingsoftware.com
softwareschoolofarts.com
softwarebond.com
esoftwareengineering.com
postflightsoftwares.com
softwareorganics.com
santiagoprogressive.com
bangaloresoftwarejobs.com
Latest News for: software progressive
TILT Releases July Update Letter From CEO
Maryville Daily Forum 10 Jul 2019
Through aggressive growth in our wholesale business in MA, to strategic pricing adjustments in Software & Services we are making great progress in reaching this goal ... TECHNOLOGY ALTERNATIVE MEDICINE HEALTH SPECIALTY AGRICULTURE NATURAL RESOURCES RETAIL SOFTWARE....
Patent shows how Microsoft's dual-screen laptop might improve its displays
TechRadar 10 Jul 2019
The patent in question, which was recently published by and spotted by Windows Latest, details a method of using multiple ambient color sensors to 'generate a single colormetric value' ... We'll just have to see, and also bear in mind that any hardware development may also depend on progress on the software front, too....
Micro Focus's first half blemished by drop in licence revenue
LONDON, July 9 (Reuters) - Britain's Micro Focus International reported a higher-than-expected 11% decline in licence revenue in its first half on Tuesday, overshadowing progress in squeezing more profit from the legacy software it provides to companies....
Elon Musk 'unhappy' with Tesla's Autopilot team: report
Market Watch 09 Jul 2019
TSLA, -0.73% Chief Executive Elon Musk is "unhappy" with the progress of developing fully autonomous vehicles, and at least 11 members of the software team have left ......
Elon Musk 'unhappy' with Tesla's Autopilot team, report says
Tesla Inc. Chief Executive Elon Musk is "unhappy" with his company's progress in developing fully autonomous vehicles, and at least 11 members of the software team have left in the past few months, according to a Tuesday report on The Information that cited one current and one former Tesla employee with knowledge of the matter ... Related ... ....
Micro Focus International plc (MFGP) CEO Stephen Murdoch on Q2 2019 Results - Earnings Call Transcript
Seeking Alpha 09 Jul 2019
This progress was driven primarily by continued cost management actions related to our integration program ... Moving now to operational highlights, we continued to make solid progress in terms of integrating HPE Software business and applying the Micro Focus model more consistently, more broadly across their operations....
Seven Years of Security: Bytecoin Marks Anniversary with New Releases
Bitcoin Garden 09 Jul 2019
This past year alone has seen a number of new features added to the ranks at Bytecoin, compounded by the release of its new Amethyst v3.4.2 software and recent hardfork. With the hardfork, Bytecoin was able to set the table for the future progression laid out for the platform in their roadmap ... About Bytecoin ... ....
Federal contractors could get favorable treatment for hiring disabled workers
Federal News Radio 08 Jul 2019
New data on Performance.gov reveals agencies made the most progress in implementing software asset management and intrusion detection and prevention capabilities over the last six months ... EPA and Energy are among the agencies struggling with implementing several capabilities including software asset management and intrusion detection and prevention....
Commvault Announces Earnings Release Date
The Record 08 Jul 2019
Eastern Time (5.30 a.m ... Commvault's converged data management solution redefines what backup means for the progressive enterprise through solutions that protect, manage, and use their most critical asset — their data. Commvault software, solutions and services are available from the company and through a global ecosystem of trusted partners ... .......
Supporting music: Moraes Foundation has donated almost $100,000 to Somerset schools
The Herald News 07 Jul 2019
SOMERSET — At the Progressive Club on Saturday, the David M. Moraes Music Foundation donated instruments, software, gift cards, scholarships and many other items to schools in Somerset.The donations were worth over $10,000 and brings the total that the foundation has ......
Why I'd ditch a Cash ISA and buy these 2 FTSE 100 dividend stocks right now
The Motley Fool 07 Jul 2019
Even though Cash ISAs offer an interest rate of just 1.5% at the very most, they remain more popular than a Stocks and Shares ISA ... BAE Systems ... BA) has moved lower ... Micro Focus. While Micro Focus (LSE ... In its recent update, the international software product group reported that it is making progress in delivering its turnaround plan ... ....
After Budget 2019, here are 10 key factors that will keep traders busy this week
Key things to watch out for would be the management commentary of its BFSI vertical, the outcome of the budgeting cycle, growth outlook for the US and European geography, progress on platform strategy, order bookings, impact of talent crunch in the US on margins and progress on localisation....
Marko: "When others weaken, we are there"
GP Blog 05 Jul 2019
"The first time they used the more aggressive engine software, it was a big step for us. But there will be another with the next engine update at Monza. "We are also progressing on the chassis at every race, so I can now say with certainty that when ......

redpajama_set_name: RedPajamaCommonCrawl


text:
Marathon Petroleum Corporation
Findlay, OH 45840-3229
https://www.marathonpetroleum.com
Sector(s): Energy
Industry: Oil & Gas Refining & Marketing
Full Time Employees:
Exercised
Year Born
Mr. Michael J. Hennigan Pres, CEO & Director 6.55M N/A 1959
Ms. Maryann T. Mannen Exec. VP & CFO 2.62M N/A 1963
Ms. Suzanne Gagle Sr. VP of Gov. Affairs & Gen. Counsel 1.8M 362.47k 1966
Mr. Carl Kristopher Hagedorn Sr. VP, Controller & Principal Accounting Officer N/A N/A 1976
Mr. Timothy J. Harris VP & Chief Technology Officer N/A N/A 1975
Ms. Kristina Anna Kazarian VP of Fin. & Investor Relations N/A N/A 1984
Ms. Molly R. Benson VP, Chief Securities, Governance & Compliance Officer and Corp. Sec. N/A N/A 1967
Ms. Fiona C. Laird Sr. VP of Communications & Chief HR Officer N/A N/A 1961
Mr. John S. Swearingen Sr. VP of Transportation and Logistics N/A N/A 1959
Mr. Brian K. Partee Sr. VP of Global Clean Products N/A N/A 1974
Amounts are as of December 31, 2021 and compensation values are for the last fiscal year ending on that date. Pay is salary, bonuses, etc. Exercised is the value of options exercised during the fiscal year. Currency in USD.
Marathon Petroleum Corporation, together with its subsidiaries, operates as an integrated downstream energy company primarily in the United States. It operates in two segments, Refining & Marketing, and Midstream. The Refining & Marketing segment refines crude oil and other feedstocks at its refineries in the Gulf Coast, Mid-Continent, and West Coast regions of the United States; and purchases refined products and ethanol for resale. Its refined products include transportation fuels, such as reformulated gasolines and blend-grade gasolines; heavy fuel oil; and asphalt. This segment also manufactures aromatics, propane, propylene, and sulfur. It sells refined products to wholesale marketing customers in the United States and internationally, buyers on the spot market, and independent entrepreneurs who operate primarily Marathon branded outlets, as well as through long-term fuel supply contracts to direct dealer locations primarily under the ARCO brand. The Midstream segment transports, stores, distributes, and markets crude oil and refined products through refining logistics assets, pipelines, terminals, towboats, and barges; gathers, processes, and transports natural gas; and gathers, transports, fractionates, stores, and markets natural gas liquids. As of December 31, 2021, the company operated 7,159 brand jobber outlets in 37 states, the District of Columbia, and Mexico through independent entrepreneurs. Marathon Petroleum Corporation was founded in 1887 and is headquartered in Findlay, Ohio.
Marathon Petroleum Corporation's ISS Governance QualityScore as of February 1, 2023 is 6. The pillar scores are Audit: 8; Board: 2; Shareholder Rights: 9; Compensation: 4.
Corporate governance scores courtesy of Institutional Shareholder Services (ISS). Scores indicate decile rank relative to index or region. A decile score of 1 indicates lower governance risk, while a 10 indicates higher governance risk.


What are SRV records? What is their function in the Domain Name System?
SRV, which is an abbreviation for Service, is a DNS record, which permits you to use a domain name for a specific service different from an Internet site. By setting up a few SRV records, you're able to use the domain name with different companies and point it to a number of servers at the same time, every single server handling a separate service. You are able to specify the port number for the connection to every machine, so there won't be any interference. You can also set individual priorities and weight for 2 records that are employed for the same service, but point to different servers for redundancy or load balancing. Using an SRV record you can use your domain address or a subdomain under it for a Voice-Over-IP server, for instance, and have the real software running on a number of machines with different providers. Which one a client of yours will use depends on the priority and weight values which you have set.
If you host a domain address in a web hosting account from our company and we handle the DNS records for it, you will be able to create a new SRV record with only a few mouse clicks within the DNS Records part of your Hepsia Control Panel. Our easy to navigate interface makes it much simpler to set up a new record compared to other web hosting Control Panels, so if you require an SRV record, you'll simply have to fill a couple of boxes and you will be ready. This includes the protocol and the port number, the value i.e. the actual record, the priority and the weight. For the last 2 you can set any value in between 1 and 100 based upon which server you want customers to access first or what instructions the other provider has given you. As an additional option, you can select how long this record is going to be active after you edit it or delete it - the so-called Time To Live time, which is measured in seconds. If you're not asked otherwise, you can leave the default value there.
Creating a new SRV record for every single domain name hosted inside a semi-dedicated server account on our end will be very easy and will require no more than just a few clicks through a user-friendly interface. Through the DNS administration tool in your Hepsia website hosting CP, you are able to create any record that you need and when you select SRV as the type, several additional textboxes will appear on your screen. There, you will have to insert the record value, the protocol, the service and also the port number and you'll be set. In addition, if the other service provider requires it, you'll also be able to set the weight and priority values when they have to be different from the standard value, which is 10. The range for these 2 options is from 1 to 100, so you have a great deal of possibilities if you use many servers for a specific service. You could also outline how long the new SRV record will remain active in case you erase it in the future by setting a TTL (Time To Live) value for it. By default, the TTL is 3600 seconds.


Just finalize the draft that student provided – correct the mistakes, the typos, and the whole picture.
Make a final selection based on the whole picture.
Low organization of research activities.
Use of the language and style of research, which close to the journalistic, and not to the scientific style.
The author of the coursework just does not have time to get to the practical application of his developments.
Inadequate use of illustrative materials, especially diagrams, charts, graphs, which give clarity and greater credibility to the content of the work.
Use the knowledge about the main mistakes in coursework writing to write your paper better. If you are using the coursework writing service, the knowledge will help you to check the quality of the final draft and, if necessary, give the requirements for the revision.
Rewrite the work, changing the structure of sentences, but living the main idea of them.
Theoretically, it is possible to change the words of synonyms for free. There are special programs that avoid plagiarism by replacing words with synonyms. On the Internet, a wide range of synonyms is available, thanks to which you can increase uniqueness. But in practice, it is not so possible to bypass antiplagiarism with this method. When you automatically replace words with synonyms, you may get an incoherent set of words. If you check the course for anti-plagiarism, then the program does not suspect anything and will give a high uniqueness, but the teacher will unlikely enjoy the result of the work. This method is good only for programs. Of course, in order to bypass the anti-plagiarism system, you can format the text yourself after the special program, but it will take a very long time.
Rewriting is the only real and effective way to increase the uniqueness of the paper. However, this method has one significant drawback: you will need a lot of free time to make it work. To rewrite the text in other words, but with preservation of meaning, will be very time-consuming. With the help of rewrites, you can increase the uniqueness and deceive plagiarism, but this is a very time-consuming method. If you are not sure of your knowledge of the subject, then you can make serious mistakes that will affect your assessment. In this case, it is better to use the coursework writing service and get the qualitative paper without plagiarism.
The procrastinator does not reveal his potential if he systematically postpones changes in life for later. A lot of time is spent on distracting maneuvers, and not on the main task. In the long term, such a strategy can cause a feeling of regret and a decrease in self-esteem. Procrastination in the workplace increases the risk of breaking deadlines or making mistakes due to haste. Such troubles spoil relations with the team and reputation. Procrastination is a result of a number of internal causes.
The most common among them are perfectionism, the lack of inner motivation, choice of immediate priorities, and fears. Efforts invested in the fight against procrastination will pay off by revealing your potential, increasing self-esteem, improving personal and professional relationships, and achieving life goals. For each type of procrastination, there are separate methods to fight against it. If you don't have an energy to fight your procrastination, you should use help of the coursework writing service.
Existential vacuum - psychoanalysis. modern deep psychology existential vacuum - psychoanalysis. modern deep psychology psychology psychoanalysis.
For independent solutions, used literature - logistics for independent solutions, used literature - logistics logistics logistics the task for.
Scientific methods in the context of discovery and in the context of substantiation of its results, method in the context of discovery - philosophy and.
Fpga i / o units, fpga interconnect systems - electronics fpga i / o units, fpga interconnect systems - electronics commodity studies electronics fpga i.
Extraction, flanging - technological processes in mechanical engineering extraction, flanging - technological processes in mechanical engineering.
Fundamentals of the theory of production, equilibrium of a firm in conditions of perfect competition - economic theory fundamentals of the theory of.
Taxpayers and features of determining the tax base and calculating and paying individual taxes when implementing agreements - taxes and taxation.
International standard on auditing 540, "audit of accounting estimates, including accounting estimates for fair value, and related disclosures".
Other derivative financial instruments, issuer options, russian depositary receipts - securities market. theory and practice other derivative financial.
The versatility of the concept of asset liquidity (asset liquidity as a reflection of the quality of market functioning) - investments the versatility of.
Inventory control systems, general characteristics of inventory control systems - logistics inventory control systems, general characteristics of.
Research of the marketing environment of the hotel enterprise, goals, directions and methods of analysis of the external environment - marketing of the.
The content of underwriting in reinsurance, conclusions - insurance underwriting the content of underwriting in reinsurance, conclusions - insurance.
Depreciation, revision of useful life, revision of depreciation method, reimbursement of carrying amount, disposal and disposal, disclosure.
Great britain, germany - multicultural education in a multinational society great britain, germany - multicultural education in a multinational society.
Social and economic functions of the rule of law in market conditions - economic basis of social work social and economic functions of the rule of law in.
Interconnected changes in stock, commodity and currency markets, responses to commodity price volatility - international finance interconnected changes.
The international banking act of 1978 of 1978 - international finance the international banking act of 1978 of 1978 - international finance finance.
Peoples of foreign europe - ethnology peoples of foreign europe - ethnology culturology ethnology (ethnography) people of the foreign europe foreign.
The term & quot; legal costs & quot; - arbitration process the term & quot; legal costs & quot; - arbitration process right arbitration process the.


text:
Landskrona es una ciudad y puerto ubicada en la costa oeste de Suecia, en el estrecho de Oresund.

Historia

La ciudad de Landskrona se fundó en Escania entonces parte de Dinamarca, el mejor puerto natural, como un medio de política anti-hanseática para el rey Erico de Pomerania, destinado a competir con los daneses ciudades bajo control hanseático.
Un monasterio de carmelitas fue fundado en 1410, donde a los comerciantes ingleses se les concedió el privilegio de una carta real en 1412, y el mismo pueblo fue fundado en 1413. Landskrona fue quemada por la Liga Hanseática en 1428.
La fundación se llevó a cabo en un lugar para un acuerdo pesquero, histórico descrito como Søndre Sæby ("Søndre" significa "sur"). Todavía hoy existe un acuerdo muy pequeño, justo al norte de la ciudad, conocido como Säby (Sæby en danés). Este fue probablemente el Nørre Sæby ("Nørre" significa "norte" en danés) en el comienzo del siglo XV, pero desde la localidad del sur se convirtió en la ciudad, la necesidad de distinguir entre el norte y el sur de Sæby desapareció. El nombre original de la ciudad fue fundada oficialmente Landszkrone. Pero cambió a Landskrone algún momento antes de 1450.
El pueblo apoyó el rey Cristián II de Dinamarca (1525), y se opuso a la Reforma en Dinamarca (1535), y en ambos casos se encontró entre los vencidos. El reformista rey Cristián III de Dinamarca se abstuvo sin embargo de las represalias, y en su lugar fundó un castillo para proteger el puerto. El castillo, construido en el monasterio había sido ubicado hasta la Reforma, se completó en 1560.

Cuando Escania fue cedida a Suecia en 1658, el puerto y la fortaleza fueron las razones para los planes de hacer Landskrona un centro comercial de los territorios adquiridos con privilegios extraordinarios para el comercio exterior. El castillo fue reforzado por bastiones, el área interior del foso extendido a 400x400 metros, el castillo fue considerado el más fuerte y más moderna en los países Escandinavos, pero se perdió temporalmente a los Daneses después de un asedio comparativamente corto del 8 de julio hasta el 2 de agosto de 1676. El comandante coronel Jerónimo Lindeberg fue sentenciado en consecuencia, a muerte por alta traición.
Había más planes para Landskrona que se tomaron en cuenta de que no obstante, por diversas razones. La continua guerra Sueca-Danesa favoreció Karlskrona, situado a una distancia segura de Dinamarca, en sustitución de Landskrona como base naval, las fortificaciones fueron suspendidos, y Malmö sigue siendo la ciudad comercial más importante - a pesar de que carecen de un puerto de Malmö hasta fines del siglo XVIII. Las fortificaciones en Landskrona se ampliaron considerablemente entre 1747 y 1788, pero fueron condenados en 1822, tras lo cual la guarnición fue abolida en 1869. Las paredes y los fosos de las fortificaciones son hoy una hermosa zona de recreo, comúnmente conocida como la Ciudadela Landskrona En su parte norte una zona de adjudicación de casas-jardín fue fundado en los años finales de los 19:. siglo. Es el más antiguo de su tipo en Suecia hoy.
Luego de la revolución industrial y urbanización de la ciudad creció rápidamente. Durante la Primera Guerra Mundial un gran astillero, Öresundsvarvet se inició. Pero después de la guerra, el rápido crecimiento de Landskrona disminuido mientras que las ciudades cercanas como Helsingborg, Lund y Malmö siguieron creciendo. A mediados de la década de 1970n el astillero tenía más de 3500 personas que trabajan - y la ciudad tenía solo 30.000 habitantes (38.000 en el municipio).
Cuando el astillero cerró en 1983 una depresión 20 años comenzó a largo. Pero poco a poco la ciudad se ha recuperado. En 2001, una nueva estación de ferrocarril se inauguró. Esto fue muy importaint para la ciudad, desde que la antigua estación era una terminal de trenes solamente hacia el sur.
La nueva estación está a lo largo del ferrocarril de doble via y alta velocidad entre Copenhague y Gotemburgo, y todos los trenes paran en la estación.
Durante muchos años había Landskrona transbordadores a Copenhague. Después de la línea de ferry última cerró en 1993 el tráfico de pasajeros con barcos de alta velocidad para el tráfico continuo de Copenhague, pero después de que el puente de Oresund, inaugurado en verano de 2000 también el tráfico de pasajeros en Copenhague terminó.

Personajes ilustres

Entre los personajes conocidos que tienen relación con Landskrona están el astrónomo Tycho Brahe, que vivió y trabajó allí entre 1576 y 1597, y la escritora Selma Lagerlöf, que trabajó como profesora, residiendo en la ciudad entre 1885 y 1895, y donde escribió su primera novela "La historia de Gösta Berling".

Actualidad

La ciudad es la única en Suecia que cuenta con trolebuses, los que fueron introducidos el año 2003.

Enlaces externos

Localidades de la provincia de Escania
Localidades portuarias de los estrechos daneses de Suecia

redpajama_set_name: RedPajamaWikipedia


I'll retry today, if AS still has issues on the contrastless crater floor I might switch back to manual MAP processing with several single point runs and insert the crater floor into the otherwise fine AS result. It looks like these captures with high frequency seeing oscillations and prominent noise are a very hard nut to crack. A bit surprising to me since I always have been amazed how good AS is tracking alignment points on almost no contrast in the footage.
Emil Kraaikamp release the first public version of his stacking tool AutoStakkert yesterday. I tried the tool with my Mars captures from April 10th. The results are a tad better than those obtained before, the contrast in the red and green channel images is noticeably higher. Quite impressing since I used the tool for the very first time. The GUI is clean and pretty self explaining and I like the functionalities: All you need to stack planetary images (without multipoint alignment) is there, the user is not bothered with things not useful.
I had to fiddle with a number of issues delaying the advancement in the project.
To continue with the project I gave up inter-thread messaging and sacrificed the separate grabber-thread. Polling frames from the camera is now done in the idle callback of the main loop and only saving data is done in a separate thread. This should still be a sufficient task splitting on a two core processor to achieve seamless captures at high framerates.


text:
require "spec_helper"

describe Colorme do
  describe ".configure" do
    let(:client_id) { "client_id" }
    let(:client_secret) { "client_secret" }
    let(:redirect_uri) { "redirect_uri" }
    let(:scope) { "read_products" }

    it "takes a block" do
      expect do
        subject.configure do
        end
      end.not_to raise_error
    end

    it "takes a block" do
      expect do
        subject.configure
      end.to raise_error
    end

    it "sets attrs" do
      subject.configure do |config|
        config.client_id = client_id
        config.client_secret = client_secret
        config.redirect_uri = redirect_uri
        config.scope = scope
      end

      expect(subject.config.client_id).to eq(client_id)
      expect(subject.config.client_secret).to eq(client_secret)
      expect(subject.config.redirect_uri).to eq(redirect_uri)
      expect(subject.config.scope).to eq(scope)
    end
  end

  describe ".authorize_uri" do
    include_context "configure colorme"

    subject { Colorme.authorize_uri }

    it "returns configured uri" do
      uri = URI(subject)
      expect(uri.scheme).to eq("https")
      expect(uri.host).to eq("api.shop-pro.jp")
      expect(uri.path).to eq("/oauth/authorize")

      query = CGI.parse(uri.query)
      expect(query["client_id"]).to eq([client_id])
      expect(query["redirect_uri"]).to eq([redirect_uri])
      expect(query["response_type"]).to eq(["code"])
      expect(query["scope"]).to eq([scope])
    end
  end
end

redpajama_set_name: RedPajamaGithub


Lakeview Cemetery is a quietly beautiful place tucked away on a hill overlooking Georgian Bay. A restful, reflective place, it's shaded by ancient trees, ornamented with carefully pruned evergreens and set off by a quiet pond enjoyed by two swans.
This weekend, as part of Culture Days, the Meaford Museum offers guided walking tours of the cemetery.
It's an opportunity to learn about the history of the largest cemetery in the Municipality, the "residents", the age-old mausoleum and much more.


I went to my first Women Who Code event tonight. It was amazing. It is always wonderful to be surrounded by doers.
It felt like a wonderful community, very diverse in skill level, experience and interest. I enjoyed my time thoroughly.
Laima, from Refinery 29, introduced me to Redux, hot loading, Webpacks and a different way to think about React components.
Erin and Angeline, two of the organizers, were very friendly and encouraging. That counts.
One of the presenters said that part of the reason that women don't stay in tech is psychological. Having a community to turn to helps. A lot.
This year privately and professionally, community is a priority. It will be a focus- deep and deliberate - to be somewhere, that matters.


text:
Giant Water Bug Stalks and Devours Fish
By Megan Gannon published 31 July 13
Scientists captured the larva of a giant water bug feeding on a small fish. The insects inject caustic digestive saliva into their prey, liquefying their meal from the inside so that they can suck out the contents. (Image credit: Nikolay Simov)
Insects are pretty low on the food chain, but there are some bugs that turn the tables, making meals out of other animals like fish and amphibians.
Scientists have captured video footage of a ferocious water bug ambushing a small fish and eating it from the inside out.
The unlikely predator, Lethocerus patruelis, is the largest European water insect, measuring more than 3 inches long (8 centimeters) in adulthood. It belongs to the Belostomatidae family of insects, which are commonly called electric light bugs or toe-biters. Their bite is considered one of the most painful to humans, but it doesn't have any harmful medical effects.
These bugs are big enough to capture and devour small crustaceans, fish and amphibians. There have even been some reports of the insects eating turtles and snakes. When they attack, the aquatic bugs inject caustic digestive saliva into their prey, liquefying their meal from the inside before they suck out the contents.
Lethocerus patruelis is found throughout the Balkan Peninsula, Anatolia, and parts of the Middle East. The researchers captured the video while studying the male reproductive system of the species. Their findings were published in the journal ZooKeys.
Follow Megan Gannon on Twitter and Google+. Follow us @livescience, Facebook & Google+. Original article on LiveScience.com.
Megan Gannon
Megan has been writing for Live Science and Space.com since 2012. Her interests range from archaeology to space exploration, and she has a bachelor's degree in English and art history from New York University. Megan spent two years as a reporter on the national desk at NewsCore. She has watched dinosaur auctions, witnessed rocket launches, licked ancient pottery sherds in Cyprus and flown in zero gravity. Follow her on Twitter and Google+.
Look up! A 'potentially hazardous' asteroid will safely zip by Earth on Jan. 18
Largest dark energy map could reveal the fate of the universe
Largest fish nursery discovered beneath Weddell Sea in Antarctica
20 of the worst epidemics and pandemics in history
Remains of a man and dog trying to escape ancient tsunami found on Aegean coast
Scientists watched a star explode in real time for the first time ever
Earth is at the center of a 1,000-light-year-wide 'Swiss cheese' bubble carved out by supernovas


text:
"Image to information" with NXT Machine Vision
Visit http://www.ids-imaging.com for further information
Industrial cameras of the IDS NXT family generate valuable information directly from image data through AI-based image processing.
06/06/19, 12:32 PM | Industrial Robotics, Mobile & Service Robots | IDS Imaging Development Systems Inc.
Intelligent, networking devices are components for future-oriented industrial processes. These cyberphysical devices communicate via standardized communication protocols to exchange valuable process information. Thanks to a powerful embedded vision platform, the industrial cameras of the IDS NXT family with modern image processing and machine learning methods are also part of this industrial revolution.
BERKSHIRE GREY RAISES $263 MILLION SERIES B FINANCING
Embedded vision: MVTec exhibits solutions at embedded world
Remke Product Catalog Available on TraceParts CAD Content Platform
Soft Robotics Announces Oversubscribed Funding Round
New Human-Robot-Collaborative (HRC-03) gripper from Zimmer Group with FreeDrive button
Pick, Purchase and Program Your First Industrial Robot
The vision app-based IDS NXT platform represents the base for a new generation of highly versatile industrial cameras from camera manufacturer IDS Imaging Development Systems GmbH. With their high-performance, freely programmable hardware in the housing of standard industrial cameras in combination with the unique vision app concept, the new IDS NXT rio & rome models are more than just image providers and represent a new evolving stage of digital industrial cameras. Powered by deep learning algorithms, they perform autonomous tasks or support PC applications or machine controllers with pre-processed data. Despite all this, they offer the functionality and data transfer performance of a standard industrial camera with GenICam interface. With this new camera family, IDS combines two devices in one.
With their app-based approach, these cameras are as versatile as smartphones. Their industry-standard camera functions can be easily extended by the user via individual image processing operations with so-called vision apps. Recurring tasks, such as reading codes, characters or number plates, as well as finding, measuring, counting or identifying objects, can be set up and changed quickly. Through "Smart GenICam", configurations, controls and results of such vision apps are also available via the camera's XML description file in any GenICam-compliant third-party application, such as HALCON. Users therefore do not have to wait long for a firmware update from the manufacturer or even look for another model because of urgently needed camera features. With Smart GenICam, even self-programmed camera functionalities can be queried and executed from any GenICam application like any other manufacturer camera feature without additional driver software. Their development completely follows the same principles as with GenICam cameras. Camera features are programmed like normal camera applications on the PC with an IDS NXT camera and converted by the vision app development kit for execution on-camera into a vision app with just a click of a button. This distinguishes the IDS NXT product families from typical smart cameras which usually have PC-like operating systems that are developed and communicated with in a completely different way to a classic industrial camera. IDS NXT, on the other hand, aims to support the working methods of each user group rather than changing them.
AI-powered image processing
The camera hardware platform is supported by a parallel working FPGA that can be reprogrammed at runtime, making the complete data path flexible to use. With a KI-Vision app developed by IDS, this integrated FPGA becomes a KI processor capable of accelerating many well-known architectures of neural networks.
Artificial neural networks now interpret complex image content with unreached accuracy and offer solutions that could not be realized by manual programming with fundamental algorithms, even with great effort. Image processing powered by artificial intelligence begins where classical image processing struggles. For instance, in order to continuously reduce error rates in a production environment, production errors must be detected and avoided at an early stage. AI-based procedures provide new, more effective approaches where it is almost impossible to predict the complete variety of possible deviations and errors completely. Using a neural network trained with a large number of sample images, the camera software can recognize known features in new image data (feature extraction). Feature relationships and weights (feature combination) then allow conclusions to be drawn about given result classes and their probabilities. With machine learning it is very easy to detect deviations (anomalies), classify objects, check surfaces for quality and defects or verify printed circuit boards and their assembly.
The diversity of neural networks is made accessible to users through a wide range of open source frameworks, high-level software and services. A multitude of published neural network architectures already cover different requirements for complexity, accuracy or inference times. Automation and monitoring of industrial plants provides more and more suitable image data for the training of these architectures.
"Image to information on-camera"
The interpreter application "IDS NXT ferry", specially developed for compatible network architectures, converts existing, already trained neural networks for use on the embedded vision platform. Users can thus conveniently provide their own neural networks to the IDS NXT inference camera for various tasks, which in addition to generating image data also directly takes care of the analysis and evaluation of this information. Determining the information content and thus a data reduction then already takes place decentrally in the camera, which avoids bandwidth bottlenecks in the data transmission. With the distribution and networking of such "cyberphysical components", direct process data will become available according to the internet of things approach, which will sustainably boost the automation and processing speed of industrial manufacturing processes.
The FPGA-based acceleration of artificial intelligence allows inference times of only a few milliseconds with common neural network architectures. Cameras based on the IDS NXT platform can thus keep pace with modern desktop CPUs in terms of accuracy and speed of results - with significantly less space and energy consumption at the same time. The re-programmability of the neural network accelerator offers additional advantages in terms of future security, low recurring costs and time-to-market. AI technology is advancing so rapidly that new frameworks and architectures are being added every month. These can be integrated by the manufacturer via software without changing the hardware platform and users do not have to purchase new devices. The fast reconfiguration of the dedicated processor also allows switching between several loaded neural networks within a few milliseconds during runtime. This enables the sequential execution of different classifications with the same image data within a vision app.
Artificial neural networks have already proven their additional value for the modern machine vision world. Machine object recognition and classification are two of the most important new capabilities that industry automation brings forward, as well as many applications in other markets. The flexible customization of the IDS NXT platform simplifies its integration into an existing system and adaptation to different markets. Equipped with this AI-based embedded system, the user can conveniently deploy his own neural networks in the inference camera for different tasks. For completely autonomous, PC-independent operation in industrial environments, model variants of the industrial cameras with industrial protocols such as PROFINET or OPC-UA will also be available. Starting in the second quarter of 2019, IDS will show an easy controllable way to quickly and easily bring AI-supported image processing to the machine as a complete embedded vision system with IDS NXT industrial cameras.
About IDS Imaging Development Systems GmbH:
The industrial camera manufacturer IDS Imaging Development Systems GmbH develops high-performance, easy-to-use USB, GigE and 3D cameras with a wide spectrum of sensors and variants. The almost unlimited range of applications covers multiple non-industrial and industrial sectors e.g. in the field of equipment, plant and mechanical engineering. In addition to its successful CMOS cameras, the company expands its portfolio with vision app-based sensors and cameras. The novel image processing platform IDS NXT is freely programmable and extremely versatile.
Since its foundation in 1997 as a two-man company, IDS has developed into a globally leading, independent, ISO-certified family business with approximately 280 employees. The headquarters in Obersulm, Germany, is used for development as well as production. With subsidiaries in the USA, Japan, South Korea and UK as well as further offices, IDS is represented internationally.
More Industrial Robotics News | Stories | Articles
Smart 3D Robot Vision with Gocator®
Easily integrate Gocator® 3D line profile and snapshot sensors with a variety of industrial robots to deliver high-performance 3D results in vision guidance, flexible inspection, material dispensing, and automated assembly with smart pick-and-place. Adding 3D vision to a robot turns repetitive, fixed motion into smart movement that can unlock greater value for your automation investment.


Salvador Custom Import Data is also a data report that includes actual shipping records. To understand the trading market, its ups & downs and even recent and past import activities of Salvador, it would be a great solution for you.
If you're a curious trader who wants to expand his/her business in Salvador, so you can take help with this!
What does it include as shipping records?
A number of records included in the Salvador Custom Import Data like the name & description of an item, harmonized system code, net weight, destination port, contact details of exporters & importers, price and so on. This database keeps all the details which are updated on a regular basis so there is no chance of skipping any important information. This import data is quite advanced and has several options that allow accessing appropriate shipping records.
Fetching Salvador Custom Import Data is not at all complicated as a lot of market research firms present out there. These companies maintain a plethora of shipping details in the form of import and export report country wise. You can select data either export or import according to your business needs. Both have different benefits but the aim is one providing actual, updated, and error-free shipment records with a user-friendly interface.
Hi everyone, I am Anjana SEAIR (a skilled and permanent write at SEAIR Exim Solutions).I had chosen Salvador Custom Import Data as today's topic of discussion. I hope you all liked it and the stuff will help you in the future.
Export Data is one such element that is very important for successful trading and the establishment of trade and commercial market. There are several companies that provide these data to the firms and companies all over India.
The article discusses in brief how business owners can get the right information by opting for custom data analysis services, as part of which experts gather, analyze and conclude valuable information from the company's database.
This is a million dollar question posed by many entrepreneurs who feel that unless pushed to the wall you don't have to seek outside resources. Do you know that from MNCs to individual Freelance Online Business the best way to make more profits is through outsourcing?
Doing an import business is not as easy as it may appear sometimes. Proper information about the market and collection of right data is important for everyone.


text:
Genome-wide profiling of RNA editing sites in sheep
Yuanyuan Zhang1,2,
Deping Han1,
Xianggui Dong1,
Jiankui Wang1,
Jianfei Chen1,
Yanzhu Yao1,
Hesham Y. A. Darwish1,3,
Wansheng Liu2 &
Xuemei Deng1
The widely observed RNA-DNA differences (RDDs) have been found to be due to nucleotide alteration by RNA editing. Canonical RNA editing (i.e., A-to-I and C-to-U editing) mediated by the adenosine deaminases acting on RNA (ADAR) family and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family during the transcriptional process is considered common and essential for the development of an individual. To date, an increasing number of RNA editing sites have been reported in human, rodents, and some farm animals; however, genome-wide detection of RNA editing events in sheep has not been reported. The aim of this study was to identify RNA editing events in sheep by comparing the RNA-seq and DNA-seq data from three biological replicates of the kidney and spleen tissues.
A total of 607 and 994 common edited sites within the three biological replicates were identified in the ovine kidney and spleen, respectively. Many of the RDDs were specific to an individual. The RNA editing-related genes identified in the present study might be evolved for specific biological functions in sheep, such as structural constituent of the cytoskeleton and microtubule-based processes. Furthermore, the edited sites found in the ovine BLCAP and NEIL1 genes are in line with those in previous reports on the porcine and human homologs, suggesting the existence of evolutionarily conserved RNA editing sites and they may play an important role in the structure and function of genes.
Our study is the first to investigate RNA editing events in sheep. We screened out 607 and 994 RNA editing sites in three biological replicates of the ovine kidney and spleen and annotated 164 and 247 genes in the kidney and spleen, respectively. The gene function and conservation analysis of these RNA editing-related genes suggest that RNA editing is associated with important gene function in sheep. The putative functionally important RNA editing sites reported in the present study will help future studies on the relationship between these edited sites and the genetic traits in sheep.
According to the central dogma, it is assumed that the sequence of mRNA truthfully reflects that of the DNA template. However, we know that the RNA sequences are not coded one-to-one by their corresponding DNA sequences. RNA modifications during co- and post-transcriptional processes contribute to the complexity of alternative splicing, and sequences and structures of the mature RNA molecules. One of the most important mechanisms is RNA editing, which results in RNA–DNA differences (RDDs), e.g., codon changes leading to protein variants [1]. It has been illustrated that the base modification at the RNA level plays an important role in post transcriptional regulation to enhance the complexity of transcripts and alter the function of genes.
The most commonly observed RNA editing event in human is A-to-I editing (normally interpreted as guanosine during transcription or by sequencing enzymes, recognized as A-to-G). The genes of the adenosine deaminases acting on RNA (ADAR) family were investigated to mediate the A-to-I editing process by binding the double-stranded (ds) RNA secondary structure [2]. Another widely described RNA editing base modification type in mammals is C-to-U conversion mediated by catalytic deaminase, apobec-1, and apobec-1 complementation factor (ACF) in apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family. The C-to-U conversion type of editing is relatively rare in the human transcriptome [3]. Both A-to-I and C-to-U events are considered as canonical RNA editing types, whereas the other types of RNA editing are generally considered as false positive detections in human genome-wide scanning studies [4,5,6]. However, there are some reports on the importance of the non-canonical editing types [7, 8].
According to the Rigorously Annotated Database of A-to-I RNA Editing (RADAR) database [9], only a few dozen human RNA editing targets that change amino acids in non-repetitive regions have been identified. An example is the initially detected RNA editing event, glutamate ionotropic receptor AMPA type subunit 2 (GluR-2) Q/R site resulting amino acid substitution, converting glutamine codon into arginine codon [10]. To date, the development of high-throughput sequencing technology such as next generation sequencing methods have facilitated the discovery of RNA editing events and its functional mechanisms in different organisms. In addition to studies on human tissues, several RNA editing sites have been reported in farm animals such as pig [11] and chicken [12].
To the best of our knowledge, there is no report on genome-wide scanning of RNA editing sites in sheep. In the present study, for the first time, we applied DNA and RNA resequencing data to identify potential editing events in sheep. We restricted our search for RNA editing sites only to homogenous genomic DNA (gDNA) sequences, but heterogenous RNA sequences as putative RDDs were also included to minimize false positives. In addition, crucial thresholds were set for the detection of RDDs for RNA and DNA mapping and genotype quality in order to eliminate uncertain reads and single-nucleotide variants (SNVs). Furthermore, we excluded the RDDs that are present on repetitive regions, which may result in mis-mapped reads and variant call errors [13, 14]. Overall, this study aims to explore reliable RNA editing events in sheep and provide more information for RNA-editing database of mammals.
The kidney and spleen tissues, and blood samples were obtained from three adult (2 years old) male Lanping sheep (a Chinese indigenous sheep breed) from the same population in Yunnan Province of China. These animals were unrelated according to their pedigree records. DNA was extracted from blood samples with the routine phenol–chloroform extraction method. The total RNA was extracted and purified using the RNA Sample Total Kit (Qiagen, German). The quality of gDNA and RNA was evaluated using NanoDrop 2000 (Thermo Fisher Scientific) and by agarose gel electrophoresis (1.2% agarose gel).
DNA/RNA sequencing
For each DNA sample, a whole-genome sequencing library was built using the Illumina TruSeq DNA Sample Preparation Kit (Illumina, Inc., San Diego, CA, USA) with an insert size of ~ 350 bp. The libraries were sequenced on the Illumina HiSeq 2000 platform. The paired-end reads of 100 bp were generated for each fragment.
The total RNA from each sample was used as input for the TruSeq RNA Prep Kit (Illumina, Inc.) and by means of indexed adapters; a sequencing library was created according to the manufacturer's instructions. RNA sequencing was conducted on the Illumina HiSeq 2500 platform, resulting in paired-end 100-bp reads. The insert length of the RNA-seq library ranged from 300 to 400 bp. The DNA- and RNA-seq data have been deposited to the National Center for Biotechnology Information (NCBI) SRA Database (accession number: SRP133430).
Mapping and variant calling strategies
The raw reads of both DNA- and RNA-seq data were first checked using the FastQC tool [15] and trimmed using Trimmomatic [16]. First six bases of each read were discarded to avoid artificial mismatches derived from random-hexamer priming, adaptors, and low-quality nucleotides (quality < 30) were also removed. The resulting clean reads were obtained and prepared for alignment against sheep reference genomic sequences (OARv4.0).
For the RNA-seq data, the reads were mapped to the sheep reference genome using the two-pass mapping strategy in STAR (v2.6) [17], and only uniquely mapped reads were extracted based on the mapping quality (MAPQ = 255). We then used the GATK ReassignOneMappingQuality read filter of GATK (v4.0.12.0) [18] to reassign map quality scores (MAPQ) of all unique alignments from 255 to the default value of 60 in GATK (v4.0.12.0) [18]. The BWA (v0.7.17) "mem" method [13] with default parameters was used to align DNA reads against the sheep reference genome (OARv4.0). The polymerase chain reaction duplicates were removed from the resulting DNA and RNA mapped bam files using the MarkDuplicates tool from GATK (v4.0.12.0) [18]. The results from the two mapping procedures were merged into a single BAM file.
Joint variant calling was conducted on the BAM file using Samtools/Bcftools [19, 20] to construct a preliminary file of known variants, which would be applied for the GATK indel realignment and base quality recalibration steps. HaplotypeCaller was then used for variant calling across all DNA and RNA alignments using the options stand_call_conf 10 and stand_emit_conf 10. According to the previous literatures, a batch of filters should be conducted to remove false positive sites resulting from sequencing and mapping bias [5, 21]. In the variant filtering step, indels were removed and only biallelic SNPs were retained for the further filtering steps. Variants that failed one of the following filters were removed: 1) alternative variants that were supported by at least two reads, 2) mapping quality score of ≥20, 3) base quality score of ≥95, and 4) strandness Fisher test value of ≤30.
Detection of putative RNA-DNA differences
In the detection of RNA–DNA differences, only positions supported by at least four genomic reads and completely homozygous were retained. The following types of mismatches were also discarded according to a previous study [5]: 1) supported by < 10 RNA-seq reads, 2) intronic mismatches located within 4 bp of a known splice junction, 3) edit ratio (fraction of edited vs. total reads) < 10% or > 95%, extremely low or high edit ratio could result from low coverage of genomic reads or sequencing error. To reduce false positives caused by sample artefact, RDDs detected in all the three biological replicates were kept and regarded as common RNA editing sites in the tissue. These types of restricted editing sites were collected and used for the further annotation.
Due to our RNA-seq data are not strandness specific, we utilized the gene annotation file (ftp://ftp.ncbi.nlm.nih.gov/genomes/Ovis_aries/GFF/) to extract the RDDs located in the transcriptional regions, and then identified their types with the help of the strand information of each transcript.
Validation of RNA-DNA differences
To validate the homozygous/heterozygous status of the putative RDDs, we used PCR to amplify RDDs on 13 putative editing sites. The PCR products of DNA and cDNA samples were sequenced by Sanger sequencing. Primers were designed using the NCBI Primer-BLAST tools (https://www.ncbi.nlm.nih.gov/tools/primer-blast/). The primer sequences are listed in Additional file 1: Table S3. The PCR reaction mixture of volume 20 μL was prepared with 1× PCR mix, 20 ng of genomic (or 5 ng of cDNA) template, and 500 nmol/L each of forward and reverse primers.
Differential expression analysis and gene annotation
Transcriptome quantification and differential expression analyses were performed using Cuffdiff [22]. ANNOVAR [23] was used to annotate the editing sites using the GFF3 files (ftp://ftp.ncbi.nlm.nih.gov/genomes/Ovis_aries/GFF/). The genes with mismatches located in the exonic regions were extracted for the functional enrichment analysis. Gene Ontology annotation were computed using the DAVID web tool [24].
To analyze the conservation of upstream and downstream sequences of an editing site, alignment of genomic sequences among different species was conducted using the alignment tool, which is available on Ensembl (https://www.ensembl.org/index.html).
Read mapping and variant calling
The trimmed reads and mapping alignments of each sample are listed in Table 1.
Table 1 Alignment of clean reads of DNA and RNA samples
After all the DNA reads of the three individuals were pooled, we estimated the average coverage of genomic sequences to be 26×. Accurate identification of variants from RNA and DNA of the same individual is the most important step in identifying RDDs. To avoid miscalled SNVs owing to sequencing errors and misalignments, we applied stringent filters (details are mentioned in methods). Transcriptome-wide screening revealed 84,361 and 97,295 high-quality heterozygous SNVs in the kidney and spleen tissues of sheep, respectively.
Identification of RNA editing
In the present study, SNV sites that were homozygous at the DNA level and heterozygous at the transcriptome level were extracted as putative RNA editing sites. After comparing the DNA-seq and RNA-seq reads generated from the same individuals and applying additional filters for removing RDDs in the splicing region, a total of 18,644 and 25,407 RDDs in the kidney and spleen were obtained, respectively. In the three kidney tissues replicates, 7,869, 6,036, and 7,779 RDDs were retained, respectively. Furthermore, 10,391, 9,253, and 10,702 RDDs were obtained from the three spleen tissue samples (Additional file 1: Figure S1). Finally, 607 common RDDs in the kidney and 994 common RDDs in the spleen were extracted as the reliable editing sites. All the putative RDDs from the three sheep individuals were listed in Additional files 2, 3 and 4.
We validated 13 RDDs by Sanger sequencing method, 9 of the 13 sites were confirmed as the true edited sites. The sites on chr11:41753132 were considered false positives by comparing their gDNA and cDNA sequencing chromatograms. At the two predicted editing sites of CARD19, two overlapping peaks were observed at the cDNA sequencing chromatograms; these peaks might result from incomplete RNA editing at these sites for all mRNA molecules in the kidney and spleen. However, the DNA sequencing of CARD19 failed, and the editing status of the two predicted sites was set as "Not sure". The chromatogram traces of gDNA and cDNA (extracted from the kidney and spleen) are shown in Additional file 1: Table S1.
The number of RDDs found in the spleen was marginally higher than that in the kidney, likely because the expression of ADAR was significantly (P< 0.01) higher in the spleen than in the kidney (Fig. 1). The adjusted fragments per kilo base per million (FPKM) sequenced read values in the spleen and kidney were 19.52 and 7.71, respectively. The expression of ADARB1 (adenosine deaminase, RNA specific B1, also known as ADAR2) was not significantly different between the kidney and spleen. The ADAR family comprises ADAR (also known as ADAR1), ADARB1, and ADARB2 (adenosine deaminase, RNA specific B2, also known as ADAR3). In human, ADAR and ADARB1 are expressed in almost all the tissues, and they have the ability to convert adenosine to inosine in double-stranded RNAs [25,26,27]. ADARB2 was not found in our sheep RNA-seq data, and it is reported to be expressed only in human brain without a known editing activity.
Normalized expression levels of ADAR and ADARB1 between the kidney and spleen tissues. Expression between the tissues was calculated by tissue-scale normalization. Pairwise t-test was used to determine the differences in the expression levels between the spleen and kidney. The ADAR expression was significantly (P < 0.05) higher in the spleen than in the kidney, but the ADARB1 expression was not significantly different between the spleen and kidney
The genomic location of RDDs
To understand the functional importance of the RDDs detected in our study, we clustered these sites according to their locations to the nearest known genes. In total, 607 and 994 RDDs in the spleen and kidney were found in all the three biological replicates simultaneously and were considered as common RNA editing sites.
Most of the common RNA editing sites in the spleen and kidney were annotated on exonic, intronic, and intergenic mismatches. One third of the RDDs in the kidney (226/607) and spleen (346/994) was found in the intergenic regions; the proportion of exonic DNA-RNA mismatches was both close to 15% in the kidney (106/607) and spleen (144/994). In the intronic regions, the mismatches in the kidney (177/607) and spleen (346/994) were made up of 27–28% RDDs in total. Especially, additional 15 and 52 mismatches were detected in ncRNAs in the kidney and spleen, respectively (Fig. 2). In addition to the common RNA editing sites, a large range of individual-specific RDDs were detected in either the spleen or kidney tissue, respectively. More than half of these individual-specific RDDs were annotated within the protein-coding and UTR regions. Irrespective of the tissues, RDDs seemed to be frequent in the UTR and protein-coding regions. In the present study, we performed further analysis on the common RNA editing sites.
Distribution of the locations of the common RDDs in kidney and spleen. Genomic location of each RDD was classified depending on the proximity to the nearest known gene. Summary of the locations of RDDs from 607 common RDDs in kidney and 994 common RDDs in spleen
Types of RDDs
Because our RNA-seq data are not strand-specific, the types of RDDs can be wrong if the types of mismatches identified in the variant detection analysis were directly used. We utilized the gene annotation file to extract the RDDs located in the transcriptional regions, and then identified their types with the help of the strand information of each transcript. The analyses of RDD types indicated that A-to-G type was the most frequent (38–46%) type of mismatches between DNA and RNA in transcriptional regions (Fig. 3). The second frequent type in transcriptional regions was T-to-C mismatches, which made up ~ 9% of the mismatches in both the kidney and spleen. The number of A-to-G mismatch was higher in the spleen (164) than in the kidney (102). This can be attributed to the fact that A-to-G editing is mainly mediated by ADAR, and the expression of which was significantly higher in the spleen than in the kidney.
Types of observed RDDs on the transcripts. 221 and 428 common RDDs were found locating on the transcriptional regions. Among the 12 types of RDDs, the most frequent event was A-to-G
Gene annotation of the common RDDs in the kidney and spleen
In total, 164 and 247 genes were annotated to the kidney and spleen RDDs (excluding intergenic RDDs), respectively. Eighty-three genes were found annotated in both the kidney and spleen RDDs. In the kidney, 44 RDDs (21 genes) in the kidney and 63 RDDs (33 genes) in the spleen were found to be nonsynonymous mutations resulting in amino acid changes or stop–gain mutations (Additional file 1: Tables S4 and S5). The enrichment analysis indicated that among the 164 and 247 genes annotated to the RDDs in the kidney and spleen, five genes related to the peroxisome term (GO:0005777) were slightly overrepresented, and the BH adjusted P value was 4.7e-2. Other RNA editing-related genes identified in the present study might be evolved in specific biological functions of sheep, such as structural constituent of the cytoskeleton and microtubule-based process, even though the BH adjusted P value was not significant. RNA editing related genes that categoried to GO terms were listed in Additional file 1: Tables S6 and S7.
Interestingly, exploration of the human RNA editing database RADAR [9] (http://rnaedit.com/download/) and the previously reported RNA editing sites, revealed that bladder cancer associated protein (BLCAP) and Nei endonuclease VIII-like 1 (NEIL1) have non-repetitive RDD sites.The type and location of the two editing sites on genomic reads and RNA reads were shown by IGV tools in Fig. 4. Further, 2,576,459 RNA editing events were recorded in the database RADAR, and 95.56% of the events were located on the ALU elements in human; 103 and 137 RNA editing-related genes in the kidney and spleen were found in the RADAR database. Among these edited genes, two edited sites in BLCAP and NEIL1 were also found in previous studies in chicken [12] and pig [28].
IGV screenshot for RNA editing sites in BLCAP (a) and BEIL1 (b). The two IGV screenshots showing the alignments of genomic and RNA reads in BLCAP (a) and BEIL1 (b). The two editing sites (NC_019470.2:65916359 and NC_019475.2:32339099) were at the center lines. From top to bottom, the tracks are as follows: genomic DNA reads, RNA reads in Kidney, RNA reads in Spleen, reference sequences and transcripts
In the present study, the editing site (amino acid change: Y/C) on exon 1 of BLCAP was found in both the kidney and spleen, and the K/R editing site on exon 6 of NEIL1 was found in the spleen of the three adult male sheep.
To investigate the conservation of regions of these RDDs between sheep and other mammal species, multiple sequence alignments of BLCAP and NEIL1 genomic sequences were performed using the Ensembl online alignment tool. The edited sites detected in BLCAP and NEIL1 were both located in conserved genomic regions with 100% sequence similarity among these species (Additional file 1: Figures S2 and S3).
RNA editing is a widespread phenomenon occurring during the co- and post-transcriptional processes. Most of the known editing sites in humans are found in non-coding regions, especially in repetitive genomic structures (for instance, the ALU elements), and in the UTRs of genes [5, 29, 30]. In our study, we used the DNA- and RNA-seq data to detect 18,644 and 25,407 RDDs in sheep kidney and spleen, however, most of the detected RDDs were individual-specific. In order to control false positives, strict detection filters were applied, such as, modest RNA-seq coverage, high quality of mapped reads and high qulity of mapped alleles. The numbers of RNA editing sites are expected to be underestimated in the present study. Many sites are edited at a low frequency and the ability to be detect comes with the increase of sequencing depth [31]. We then focused on RDDs located on UTRs and protein coding regions, which are considered to be likely correlated with gene functions. There should be more number of editing sites in sheep than that identified in the present study, because we only focused on RDDs and used restrictive filtering parameters to minimize noise; thus, we provided some reliable RNA editing sites in sheep, but inevitably we missed some true sites.
Generally, among all the RDD types, A-to-I and C-to-U are presumed to be canonical editing sites; the other 10 non-canonical editing sites were usually presumed to be false-positive results due to the current sequencing technology and analysis limitations [5].
Some studies have indicated that both canonical and non-canonical editing sites exist in the transcriptome [32]. The C-to-T editing mediated by the APOBEC family has been found to increase the number of C-to-T and G-to-A mismatches, because the C-to-U editing sites can produce C-to-T editing in the primary strand, whereas G-to-A editing occurs on the complementary strand [33]. Similarly, A-to-I editing might increase the A-to-G and T-to-C mismatches. Our transcriptomic data showed that APOBEC1 is not expressed in the two tissues investigated, but APOBEC2 and APOBEC3F were found to be expressed at a low level (Additional file 1: Table S2). Furthermore, we observed other non-canonical RNA editing sites, such as G-to-A and T-to-C in both the kidney and spleen. This can be attributed to the fact that our RNA-seq data were not strand-specific. Moreover, the type of a RDD has a high probability of being erroneously called to be a different type. Additionally, RDDs identified from RNA-seq reads covering or intersecting with known genes can be assumed to originate from these genes. Thus, the percentage of RDD type within known genes were estimated, however, RDDs in unannotated regions or in regions with bidirectional transcription were not taken into any categories. The results showed that A-to-G type was the most frequent (38–46%) type of mismatches between DNA and RNA in transcriptional regions. Future study with strand-specific RNA-seq is needed to confirm the non-canonical RNA editing sites identified in the present study.
Tissue-specific edited sites might play important roles in regulating gene expression
The RNA editing events that result in changes in amino acid residues are prevalent regulation changes of phenotypes, and the widespread RNA editing events are known to play an important role in the diversity of the transcriptome by producing presumably more types of transcripts, while affecting only a few nucleotides [34]. In the present study, we identified 18,644 and 25,407 RDDs in the kidney and spleen of sheep, respectively. More than 90% RDDs showed tissue or individual specificity, indicating that the large proportion of physiological differences among individuals and tissues might be attributed to the diversity in the transcriptional and post-transcriptional processes. A previous study has also suggested that RDDs show cell or tissue specificity during development; they are probably not functionally important because of their rare occurrence within populations [27]. Conversely, common editing sites can be associated with certain advantages and hence are preserved during evolution [5]. RNA editing can alter gene expression by affecting the binding of small regulatory RNAs (microRNAs and siRNAs), creating alternative splice sites, and changing the sites in stop codons [35, 36]. Therefore, the editing sites might be important for the variation in gene expression and phenotypic features.
Conserved edited sites in BLCAP and NEIL1
Within all the three biological replicates, 75 genes were found containing reliable RNA editing sites in sheep. Two edited sites in BLCAP and NEIL1 are also reported in other species. Furthermore, the sequences near the edited sites in BLCAP and NEIL1 have high similarities among mammal species (Additional file 1: Figures S2 and S3), suggesting that these editing events might be conserved in mammals.
BLCAP, a highly conserved gene with tumor-suppressor function in different carcinomas, was previously identified as an edited gene in the brain [37] and fat tissue of pig [11], and the same Y/C editing site is mapped in the key YXXQ motif in human. BLCAP with RNA editing at this site was found to lose its ability to inhibit signal transducer and activator of transcription 3 (STAT3), providing a clue that the Y/C editing site in BLCAP is associated with the function of BLCAP and the development of cancer [38]. Exon 6 K/R RDD found in the present study in the sheep NEIL1 gene, which codes for a DNA repair enzyme, has also been reported in multiple tissues in human [39] and pig [11]. Additionally, it has been reported that the edited and unedited forms of the NEIL1 proteins have distinct enzymatic properties for glycosylase activity and lesion specificity, and the editing level can be regulated extracellularly by interferon [40].
These editing events occur in the protein coding region can directly alter the protein sequences and structures, and then affect the biological function. These results suggest a specific regulatory mechanism for gene function derived by RNA editing.
To the best of our knowledge, our study is the first to detect RNA editing in sheep by comparing RNA-seq and DNA-seq data from three biological replicates of the kidney and spleen tissues. Under stringent sequence data filters, a total of 607 and 994 common RDDs were identified in the ovine kidney and spleen as the reliable RNA editing sites. Further,164 and 247 genes were annotated to the kidney and spleen RDDs. The amino acid conversion edited sites found in the ovine BLCAP and NEIL1 are conserved in pig and human, suggesting that evolutionarily conserved RNA editing sites may be important for gene function and the development of an individual. Our study provides some putative functionally important RNA editing sites in sheep, and it is important to conduct further studies to reveal the functional changes in RNA editing event genes and their roles in economically beneficial traits and diseases in sheep.
ADAR:
Adenosine deaminases acting on RNA
cDNA:
ds:
Double-stranded
FPKM:
Fragments per kilo base per million
gDNA:
MAPQ:
Map quality score
Rigorously Annotated Database of A-to-I RNA Editing
RDD:
RNA-DNA difference
SNP:
Single nucleotide polymorphism
SNV:
Single-nucleotide variant
Untranslated region
Gott JM, Emeson RB. Functions and mechanisms of RNA editing. Annu Rev Genet. 2000;34:499–531.
Slotkin W, Nishikura K. Adenosine-to-inosine RNA editing and human disease. Genome Med. 2013;5:105.
Rosenberg BR, Hamilton CE, Mwangi MM, Dewell S, Papavasiliou FN. Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs. Nat Struct Mol Biol. 2011;18:230–6.
Park E, Guo J, Shen S, Demirdjian L, Wu YN, Lin L, et al. Population and allelic variation of A-to-I RNA editing in human transcriptomes. Genome Biol. 2017;18:143.
Zhang Q, Xiao X. Genome sequence-independent identification of RNA editing sites. Nat Methods. 2015;12:347–50.
Ramaswami G, Lin W, Piskol R, Tan MH, Davis C, Li JB. Accurate identification of human Alu and non-Alu RNA editing sites. Nat Methods. 2012;9:579–81.
Rubio MAT, Paris Z, Gaston KW, Fleming IMC, Sample P, Trotta CR, et al. Unusual noncanonical intron editing is important for tRNA splicing in Trypanosoma brucei. Mol Cell. 2013;52:184–92.
Zheng Y, Ji B, Song R, Wang S, Li T, Zhang X, et al. Accurate detection for a wide range of mutation and editing sites of microRNAs from small RNA high-throughput sequencing profiles. Nucleic Acids Res. 2016;44:e123.
Ramaswami G, Li JB. RADAR: a rigorously annotated database of A-to-I RNA editing. Nucleic Acids Res. 2014;42:D109–13.
Sommer B, Kohler M, Sprengel R, Seeburg PH. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991;67:11–9.
Funkhouser SA, Steibel JP, Bates RO, Raney NE, Schenk D, Ernst CW. Evidence for transcriptome-wide RNA editing among Sus scrofa PRE-1 SINE elements. BMC Genomics. 2017;18:360.
Fresard L, Leroux S, Roux PF, Klopp C, Fabre S, Esquerre D, et al. Genome-wide characterization of RNA editing in chicken embryos reveals common features among vertebrates. PLoS One. 2015;10:e0126776.
Li H, Durbin R. Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics. 2009;25:1754–60.
Robasky K, Lewis NE, Church GM. The role of replicates for error mitigation in next-generation sequencing. Nat Rev Genet. 2014;15:56–62.
Andrews S. FastQC- A quality control tool for high throughput sequence data. https://www.bioinformatics.babraham.ac.uk/projects/fastqc/.
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–20.
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.
DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43:491–8.
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25:2078–9.
Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011;27:2987–93.
Lee JH, Ang JK, Xiao X. Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants. RNA. 2013;19:725–32.
Trapnell C, Hendrickson DG, Sauvageau M, Goff L, Rinn JL, Pachter L. Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat Biotechnol. 2013;31:46–53.
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.
Huang d W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.
Grice LF, Degnan BM. The origin of the ADAR gene family and animal RNA editing. BMC Evol Biol. 2015;15:4.
Terajima H, Yoshitane H, Ozaki H, Suzuki Y, Shimba S, Kuroda S, et al. ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm. Nat Genet. 2017;49:146–51.
Nishikura K. Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem. 2010;79:321–49.
Levanon EY, Eisenberg E, Yelin R, Nemzer S, Hallegger M, Shemesh R, et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol. 2004;22:1001–5.
Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, et al. Widespread RNA and DNA sequence differences in the human transcriptome. Science. 2011;333:53–8.
Huntley MA, Lou M, Goldstein LD, Lawrence M, Dijkgraaf GJ, Kaminker JS, et al. Complex regulation of ADAR-mediated RNA-editing across tissues. BMC Genomics. 2016;17:61.
Bahn JH, Lee JH, Li G, Greer C, Peng G, Xiao X. Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. Genome Res. 2012;22:142–50.
Hamilton CE, Papavasiliou FN, Rosenberg BR. Diverse functions for DNA and RNA editing in the immune system. RNA Biol. 2010;7:220–8.
Goldstein B, Agranat-Tamir L, Light D, Ben-Naim Zgayer O, Fishman A, Lamm AT. A-to-I RNA editing promotes developmental stage-specific gene and lncRNA expression. Genome Res. 2017;27:462–70.
Jepson JE, Reenan RA. RNA editing in regulating gene expression in the brain. Biochim Biophys Acta. 2008;1779:459–70.
Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science. 2007;315:1137–40.
Veno MT, Bramsen JB, Bendixen C, Panitz F, Holm IE, Ohman M, et al. Spatio-temporal regulation of ADAR editing during development in porcine neural tissues. RNA Biol. 2012;9:1054–65.
Chen W, He W, Cai H, Hu B, Zheng C, Ke X, et al. A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer. Oncotarget. 2017;8:39417–29.
Picardi E, Manzari C, Mastropasqua F, Aiello I, D'Erchia AM, Pesole G. Profiling RNA editing in human tissues: towards the inosinome atlas. Sci Rep. 2015;5:14941.
Yeo J, Goodman RA, Schirle NT, David SS, Beal PA. RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1. Proc Natl Acad Sci U S A. 2010;107:20715–9.
We thank Dr. Weidong Deng and Dr. Xiao Gou of the Yunnan Agricultural University for providing a portion of the tissue samples.
This study was funded by the National Nature Science Foundation of China (U1136605), Ningxia Agricultural Breeding Program (NXNYYZ20150103), and Program for Changjiang Scholar and Innovation Research Team in University (IRT1191).
The raw reads of DNA and RNA samples are available on the NCBI SRA database (accession number: SRP133430).
Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture & Beijing Key Laboratory of Animal Genetic Improvement, China Agricultural University, Beijing, 100193, China
Yuanyuan Zhang, Deping Han, Xianggui Dong, Jiankui Wang, Jianfei Chen, Yanzhu Yao, Hesham Y. A. Darwish & Xuemei Deng
Department of Animal Science, Pennsylvania State University, University Park, PA, 16802, USA
Yuanyuan Zhang & Wansheng Liu
Animal Production Research Institute, Agricultural Research Center, Ministry of Agriculture and Land Reclamation, Giza, 12618, Egypt
Hesham Y. A. Darwish
Yuanyuan Zhang
Deping Han
Xianggui Dong
Jiankui Wang
Jianfei Chen
Yanzhu Yao
Wansheng Liu
Xuemei Deng
YYZ, WSL, and XMD conceived and designed the experiments, and wrote and modified the manuscript. DPH, JKW, JFC, and HYAD prepared the DNA and RNA samples and performed PCR validation experiments. YYZ, XGD, and YZY performed data analysis. All authors read and approved the final manuscript.
Correspondence to Wansheng Liu or Xuemei Deng.
Three male sheep were obtained from the local farm in Lanping, Yunnan Province, China. All animal experiments were approved by the Beijing Administration Committee of Laboratory Animals and conducted in accordance with the China Agricultural University (CAU) Institutional Animal Care and Use Committee guidelines (ID: SKLAB-B-2010–003). The protocols for animal use and experimentation were approved by the Beijing Association for Science and Technology (approval ID SYXK [Beijing] 2007–0023) and were in compliance with the Beijing Laboratory Animal Welfare and Ethics guidelines.
Figure S1. Shared RDDs of the Three Biological Replicates in the Kidney and Spleen. Figure S2. Conservation Analysis of BLCAP. Figure S3. Conservation Analysis of NEIL1. Table S1. Validation of RNA Editing Sites by Sanger Sequencing. Table S2. FPKM (mean ± SD) of APOBEC3F and APOBEC2 in the Kidney and Spleen. Table S3. PCR Primers Used in Sanger Sequencing Validation. Table S4. Nonsynonymous Common Editing Sites in the Kidney of Sheep. Table S5. Nonsynonymous Common Editing Sites in the Spleen of sheep. Table S6. Functional Annotation Results of RNA Editing Genes in the Kidney of sheep. Table S7. Functional Annotation Results of RNA Editing Genes in the spleen of sheep. (DOCX 1050 kb)
Putative RDDs in Sheep Individual1. (XLSX 1098 kb)
Putative RDDs in Sheep Individual2. (XLSX 880 kb)
Zhang, Y., Han, D., Dong, X. et al. Genome-wide profiling of RNA editing sites in sheep. J Animal Sci Biotechnol 10, 31 (2019). https://doi.org/10.1186/s40104-019-0331-z
DOI: https://doi.org/10.1186/s40104-019-0331-z
DNA resequencing
RNA-DNA differences
RNA editing


Learners: explains how to complete peer review & view feedback from peers for Individual Project, Group Project, Q&A, and Interactive Video. To ensure the best experience possible, please follow our Basic System Requirements.
You may have the option to review other learners' submissions.
For a preview of this workflow, view the video below. Please note, there is no voiceover for this video.
The default setting is to allow peer review only after you complete the assignment. After your submission, peer review will be at the top of the assignment window.
Depending on the instructor's settings, peer review may be available before you complete the assignment. In this case, peer review will be at the bottom of the assignment window.
You can leave comments on submissions*. The comments box is to the right of your peers' videos.
*Your instructor may elect to make your comments anonymous.
To add a video comment, select the Camera icon and record your video. You can record up to 15 minutes of video feedback.
To add a text comment, click into the text box and start typing. There is a 2,048 character limit for text comments.To submit the text comment, click the Send icon.
Depending on your instructor's settings, you will review a peer's submission with either 1) a 5-star rating or 2) a rubric. You may also have the option to self-assess.
You can give 5-star ratings below the commenting section. Select the number of stars that corresponds with your evaluation.
If your instructor has enabled a rubric for peer review*, the rubric score will be at the bottom of the commenting section.
Grade the submission using the rubric criteria, then Save.
When rubric option is enabled, your instructor may give you the option to assess your own video. If this is the case, you will complete the rubric as you did for your peer's videos.
At the bottom of the page, you can view feedback left on your submission from both peers and instructors. While you play your video, time-stamped SyncComments will appear.
Your final grade from your instructor will appear at the top of the screen.