Two sessions on Sunday at Heritage Christian

July will bring Dave Matthews, Foo Fighters and Janelle Monae to Indianapolis, plus Heartland's first short-film festival.

Two days ago Mario Hidalgo, CEO of the Spanish airline “Hola Airlines“ , announced that Hola Airlines (Baleares Link Express SL) has been obliged by the US government to stop its operations in Cuba . The US Government threatened Hola Airlines via Boeing to end the service of maintenance of the Boeing aircraft belonging to the [...]

Pioneer is not closed and a new menu is coming soon.

Indy has a range of high-altitude hotspots, and more are in the works.

Loco Mexican Restaurant to fill space where LongBranch, 22nd Street Diner failed.

Whether it's out of necessity, to pass time or to calm nerves, bread baking is a hot topic during coronavirus pandemic

Former Celtic goalkeeper Jonathan Gould and ex-striker Harald Brattbakk relive the club's memorable 1998 title success.

Teams will be allowed to use five substitutes when the season resumes after a Fifa proposal to help with fixture congestion was approved.

Despite the recent fatalities, the county's observed mortality rate associated with COVID-19 remained at about 2.1% — still significantly lower than the state's, which is roughly 4%.

The DOJ ordered an Orange County company to stop distributing hand-sanitizer products until it got FDA approval or removed certain claims from its labeling.

Police are encouraging the public to know their rights if they’re stopped on the road after two authentic police badges were stolen from a home in Waterloo Region earlier this week.

Italy has the third highest officially recorded coronavirus deaths, after the US and the UK.

Scientists say the microbe - found in the wild near Lake Victoria - has enormous potential.

The essential things to consider when buying a laptop

Goff started the season with 941 yards and six touchdowns over his first three games then completed 26 of his 33 passes against the Minnesota Vikings for 465 yards and five touchdowns in Week 4.

Anderson has had to face Darius Slay, Xavien Howard, Denzel Ward and Jalen Ramsey in coverage during the first four weeks of the season. Better days should be ahead, starting next week against the Colts.

Goff is using play-action more often than any other quarterback in 2018.

Mack carried the ball 19 times for 126 yards and a touchdown and added two catches for 33 yards and a touchdown on Sunday against the Bills.

The dismissal of coach Hue Jackson seems to have given Duke Johnson Jr. new life with the Browns.

Michigan, Georgia and Oklahoma scrambling for final spots.

Washington will be without their starting right guard, right tackle, left guard, left tackle, center and starting quarterback on Sunday, making the Dallas defense a very solid pickup.

Since 2002, the first year the league expanded to 32 teams, the Chargers have made the playoffs six times, just one of which saw them advance further than the divisional round. That could change this season.

• Every week, Parrot Analytics provides Business Insider with a list of the nine most in-demand original TV shows on streaming services in the US.
• This week includes "The Midnight Gospel," a surprise animated hit from Netflix. 
• Visit Business Insider's homepage for more stories.

Netflix's new animated series, "The Midnight Gospel," is a surprise hit and gaining in audience demand while the one-time sensation, "Tiger King," dramatically dipped to the point where it's not among this week's most in-demand streaming originals. 

Every week, Parrot Analytics provides Business Insider with a list of the nine most in-demand TV shows on streaming services in the US.

The data is based on "demand expressions," Parrot Analytics' globally standardized TV-demand measurement unit. Audience demand reflects the desire, engagement, and viewership weighted by importance, so a stream or a download is a higher expression of demand than a "like" or a comment on social media, for instance.

Disney Plus' final season of "Star Wars: The Clone Wars" dramatically surged in demand this week after the series finale debuted on May 4, otherwise known as "Star Wars" Day.

But last week's newcomers, Apple TV Plus' "Defending Jacob" and Hulu's "Little Fires Everywhere," disappeared this week. 

SEE ALSO: Insiders say major questions hang over DC Universe as its parent company prepares to launch Netflix rival HBO Max

9. "The Midnight Gospel" (Netflix)

Average demand expressions: 32,846,492

Description: "Traversing trippy worlds inside his universe simulator, a space caster explores existential questions about life, death and everything in between."

Rotten Tomatoes critic score (Season 1): 90%

What critics said: "We often say that a show is 'like nothing else on television' and it's usually an act of critical hyperbole. Trust me. It's true here." — RogerEbert.com (Season 1)

Season 1 premiered on Netflix on April 20. See more insights here.

8. "Narcos: Mexico" (Netflix)

Average demand expressions: 33,194,298

Description: "Witness the birth of the Mexican drug war in the 1980s as a gritty new ‚Narcos' saga chronicles the true story of the Guadalajara cartel's ascent."

Rotten Tomatoes critic score (Season 2): 87%

What critics said: "The second season of Narcos: Mexico, then, is far from flawless - but there are enough reminders of what has made the show such a phenomenon to make it a worthy watch." — Radio Times (Season 2)

Season 2 premiered February 13 on Netflix. See more insights here.

7. "The Witcher" (Netflix)

Average demand expressions: 34,076,054

Description: "Geralt of Rivia, a mutated monster-hunter for hire, journeys toward his destiny in a turbulent world where people often prove more wicked than beasts."

Rotten Tomatoes critic score (Season 1): 67%

What critics said: "It is messy, and absurd, but also — it is fun." — The Atlantic (Season 1)

Season 1 premiered on Netflix on December 20. See more insights here.

6. "Harley Quinn" (DC Universe)

Average demand expressions: 34,470,458

Description: "Harley Quinn has taken down the Joker and Gotham City is finally hers for the taking…whatever's left of it that is. Gotham has become a desolate wasteland, left in ruins, following the huge earthquake caused by the collapse of Joker's tower. Harley's celebration in this newly created chaos is cut short when Penguin, Bane, Mr. Freeze, The Riddler, and Two-Face join forces to restore order in the criminal underworld. Calling themselves the Injustice League, this group now stands in the way of Harley and her crew from taking sole control of Gotham as the top villains of the city."

Rotten Tomatoes critic score (Season 2): 88%

What critics said: "If you weren't sold on the first season of Harley Quinn, the Season 2 premiere probably won't change your mind. However, the series looks to be even stronger in its sophomore outing." — IGN (season 2)

Season 2 premiered April 3 on DC Universe. See more insights here.

5. "Titans" (DC Universe)

Average demand expressions: 40,950,684

Description: "'Titans' follows young heroes from across the DC Universe as they come of age and find belonging in a gritty take on the classic Teen Titans franchise. Dick Grayson and Rachel Roth, a special young girl possessed by a strange darkness, get embroiled in a conspiracy that could bring Hell on Earth. Joining them along the way are the hot-headed Starfire and lovable Beast Boy. Together they become a surrogate family and team of heroes."

Rotten Tomatoes critic score (Season 2): 81%

What critics said: "This hard-hitting drama provided much of the talented cast with some juicy material, while also allowing the show to continue to go from strength-to-strength." — What Culture (Season 2)

Season 2 premiered on DC Universe on September 6. See more insights here.

4. "Money Heist (La Casa de Papel)" (Netflix)

Average demand expressions: 45,905,200

Description: "Eight thieves take hostages and lock themselves in the Royal Mint of Spain as a criminal mastermind manipulates the police to carry out his plan."

Rotten Tomatoes critic score (Season 4): 75%

What critics said: "If you are looking for addictive entertainment, this fourth season of 'Money Heist' has more than enough doses of it." — Espinoff (Season 4)

Season 4 premiered on Netflix April 3. See more insights here.

3. "The Mandalorian" (Disney Plus)

Average demand expressions: 53,820,742

Description: "After the fall of the Empire, a lone gunfighter makes his way through the lawless galaxy."

Rotten Tomatoes critic score (Season 1): 93%

What critics said: "[The Mandalorian] has an empire of sentiment serving as the wind at its back, and as long as it keeps up its momentum, even those of us programmed to dissect and critique programs may be content to simply sail along with it." — Salon (Season 1)

Season 1 premiered on Disney Plus on November 12. See more insights here.

2. "Stranger Things" (Netflix)

Average demand expressions: 57,853,672

Description: "When a young boy vanishes, a small town uncovers a mystery involving secret experiments."

Rotten Tomatoes critic score (Season 3): 89%

What critics said: "Even the most distinctive moments feel disconnected from the rest, especially a segment in the final episode that feels as if its sole purpose is to be extracted and recirculated as a meme." — Slate (Season 3)

1. "Star Wars: The Clone Wars" (Disney Plus)

Average demand expressions: 126,320,893

Description: "From Dave Filoni, director and executive producer of 'The Mandalorian,' the new Clone Wars episodes will continue the storylines introduced in the original series, exploring the events leading up to 'Star Wars: Revenge of the Sith.'"

Rotten Tomatoes critic score (Season 7): 100%

What critics said: "The overall ending to seven seasons can feel rudely abrupt when other threads are hanging. But the solemn meditation on the casualties of war and the slow-yet-swift-feeling disintegration of a seemingly secure world is the microcosm of the entire series." — Slashfilm (season 7)

Season 7 premiered on February 21 on Disney Plus. See more insights here.

The Fox Nation host got plenty of criticism for her tweet about the Democratic presidential candidate — including from fellow Fox-ers.

A discussion about the impeachment hearings turned into a showdown between the co-hosts.

I reveal my top and best cruise hacks, tips and tricks that will help you make the most of your cruising vacation in 2019 and 2020. These cruising tips are things that I have learnt to help me get better cruise fares, save money on board a cruise ship, pack better and smarter, find the best cabin, find and save money on excursions and lots more. These are all proven and should help you. Enjoy these cruising hacks, tips and tricks.

** Subscribe to my channel: http://bit.ly/TFT_YouTube2
** Buy one of my unique Cruise T-shirts: http://bit.ly/TFTStore
** Get great cruise deals via CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise

Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises.

Follow Tips For Travellers on:
- Instagram: http://www.instagram.com/garybembridge
- Facebook: http://www.facebook.com/tipsfortravellers
- Twitter: http://www.twitter.com/garybembridge

oscon: RT @mark_grover: Attending #oscon at end of July in Portland? Come hear my talk on Apache Bigtop http://t.co/kkSdOyyY5a

oscon: Tutorials at #OSCON are filing up (some already sold out). Register soon to get your top choices http://t.co/bQv7k8VXTf

The Public Investment Corporation has terminated the employment contract of Executive Head of Listed Investments Fidelis Madavo, it said in a statement on Monday.

As US states reopen, White House keeps CDC guidance on the shelf | Trump tests negative after valet contracts virus; here are the top world news videos for today. WATCH.

Russia has registered more than 10 000 new coronavirus cases for the sixth day in a row, after emerging as a new hotspot of the pandemic.

Eat baked potatoes on the regular? Make your baked potatoes a meal with these winning combos and recipes for toppers!

Continue reading "10 Ways to Top a Baked Potato" »

Sen. Ted Cruz was apparently about to get into mullet territory. He hadn’t had a haircut in three months. Things were looking grim for the Texas senator. Thankfully, Shelley Luther is able to do something about that. Luther is both famous and free after a viral clip of her standing up to a judge who…

The post Ted Cruz Stops by Shelly Luther’s Salon for a Trim, ‘True Authenticity’ Leaves Her Sobbing appeared first on The Western Journal.

BEST DEALS ON GAMING LAPTOPS:

• MSI - Modern 15 15.6" Laptop — $749

• ASUS - ROG G531GT 15.6" Gaming Laptop — $999.99

• Dell - G3 15.6" Gaming Laptop — $999.99

It's time to level up.

If you didn't already know, PC gamers take great pride in the way they play. These are the folks who delight in the fact that PC gaming is just so much better than playing on a console, and if this Reddit thread is any indication — this way of thinking isn't going away any time soon.

While it can take a year or two for gaming consoles to adapt to updated technology, PCs see that improvement hit almost instantly. New rigs and laptops hit the market faster, as opposed to consoles that make you wait for months until their release.  Read more...

BEST DEALS ON GAMING LAPTOPS:

• MSI - Modern 15 15.6" Laptop — $749

• ASUS - ROG G531GT 15.6" Gaming Laptop — $999.99

• Dell - G3 15.6" Gaming Laptop — $999.99

My first gaming laptop cost $1,500 more than 10 years ago, and that was considered affordable. It wasn't a top-of-the-line model, but it wasn't a slouch either, sporting one of the better mid-tier graphics cards and a reliable processor/RAM combination.  

But my, how things have changed.

Today, you can go on Amazon and find plenty of laptops for less than $1,000 that would have been at least $1,500 a few years ago, thus opening doors to people who want to try out PC gaming for themselves. (And if it's Prime Day or Black Friday or Cyber Monday, you can expect deal prices to dip even lower.) But sorting through all of the options and deciding which is best presents its own unique challenge. Read more...

Internet of Yum digs into all the things that make us drool while we're checking our feeds.

The famously sensitive strongman, actor Terry Crews, is screaming at the top of his lungs. In another time and place, you would be sure he was getting tortured. Which, essentially he is — just not as a form of punishment. Instead, the misery is all in the name of promotional entertainment, with Crews' self-inflicted tears generating views for the YouTube series Hot Ones.

Across the centuries, people have watched transfixed as others dare to eat disgusting, torturous, or sickening amounts of food. The specifics change with the venue, but it is a consistent form of entertainment.  Read more...

Like what you see? We’d love you to Share, Like, and Comment on Facebook! Conservative Intel has partnered with Pat Cross Cartoons! Pat loves drawing, America, and the Big Man upstairs. His work aims to combine these three elements into a petri dish and see what happens. We hope you will find his work thought-provoking, insightful, profound, and […]

The post Unstoppable appeared first on Conservative Intelligence Briefing.

Decision-making can be tough especially when the best choice isn’t glaringly obvious. We’re faced with this process every minute of the day. When do I wake up? What’s for lunch? Do I want to go out on a date with this person? What do I want to do with my life? Can I stay in […]

The post Stop Losing Sleep: 7 Steps for Stress-free Decision-making appeared first on Dumb Little Man.

Michael Tiffany, co-founder and president of ad verification and fraud prevention firm White Ops, discusses the next evolution of fraudulent practices for 2018.

Amazon’s share of US ecommerce approaches 40% February 24, 2020 (New York, NY) — Target’s increased focus on building its ecommerce business has been paying off. The big-box retailer, which […]

Travel is fun, when you plan things properly. If you have visited many countries, then surely you have made many mistakes such as booking resorts at wrong places or buying costly souvenirs which are easily available in your country. We all make silly mistakes when we visit a new country and there is no need to feel ashamed. What you need to do is make sure that you don’t repeat those mistakes.

When it comes to mistakes, I am not talking about flight or hotel ticket booking blunders. There are many more small oversights that can ruin your vacation. Let’s explore some of the common mistakes that tourists make every year.

No research about the place: You may know the name of the country, its capital and its currency exchange rate, but do you really know the place you are visiting? For example, in India, there are many prepaid taxi booths that charge right amount for a trip, but if you just pick any cab from the road, the driver may charge you double because you don’t know the route to your destination. Similarly, it is important to know the things you can and can’t do in the place you are visiting. For example, taking pictures is prohibited in many religious places.

Over-packing: Never carry too many clothes, because you are going to carry your bags, and if those are too heavy, you will curse yourself. Besides, the airlines charge hefty amount if your luggage crosses the weight limit. Always pack only those things that are necessary for the place you are visiting. For example, if you are going to Tadoba tiger reserve forest and staying at Tadoba tiger resort, then you don’t need to pack a cocktail party dress. It is better to pack a few jeans and t-shirts.

Speaking English only: Try to learn a few sentences in the local language. For example, words of greetings, how to ask for road directions and how to ask the price of something. The more you communicate with the locals in their own language, the more confident you will feel.

Disrespecting the customs: India is a conservative county, and the culture of Indians is very different from Americans. However, that does not mean you can mock or disrespect their culture. For example, Americans enter churches wearing shoes, but in India, you can’t wear shoes in a temple. Respect the rule while visiting any temple in India. After all, you are visiting a new country to understand its culture.

Reading guidebooks only: Guidebooks are for references and they can’t give you all the information about the place. For example, a guidebook may tell you that Taj Mahal is wonderful, but unless you raise your face from the book, can you truly appreciate its beauty?

Booking hotels and flights separately: Take a look at the famous travel portals and you will find that they are offering great hotel + airplane deals. When you book return tickets and also hotel rooms, you can save a few hundred dollars. Besides, it is a hassle free process as you are getting everything from one site.

Interrupting the guide: You can be the history professor in a college, but if you interrupt the guide when he is talking about a historical place, then you are being rude. All the other tourists have paid for the guided tour and by interrupting the guide frequently you are making everyone angry.

So, when you visit a foreign country this year, make sure that you don’t make the mistakes mentioned above. Enjoy nature, history and culture of the place you are visiting and you will feel rejuvenated by the end of your vacation.

If you like traveling to exotic places, check out our Machu Picchu Tours page

In a classic bit from an early Seinfeld, Jerry and Elaine are at the airport, trying to pick up the rental car that Jerry had reserved. As usual, things go poorly and get awkward fast:

Seinfeld - "Reservations"

JERRY: I don't understand...I made a reservation. Do you have my reservation?
AGENT: Yes, we do. Unfortunately, we ran out of cars.
JERRY: But, the reservation keeps the car here. That's why you have the reservation.
AGENT: I know why we have reservations.
JERRY: I don't think you do. If you did, I'd have a car. See, you know how to take the reservation--you just don't know how to hold the reservation. And, that's really the most important part of the reservation...the holding. Anybody can just TAKE them. [grabs chaotically at air]

And, how weirdly similar is that to our conflicted relationship with New Year's resolutions?

In Seinfeldspeak?

See, you know how to make the resolution, you just don't know how to keep the resolution. And, that's really the most important part of the resolution...the keeping. Anybody can just MAKE them!

Oversimplified? Probably.

But, ask yourself. Why this? And, why now? Or, why again?

Welcome to Resolvers Anonymous: I'm 'Merlin M.'

A few years ago, I shared a handful of stories on the failures that have led to my own cynicism about the usefulness of life-inverting resolutions. Because, yeah, I've historically been a big resolver.

Here's what I said when I first suggested favoring "Fresh Starts and Modest Changes" over reinventions:

Download MP3 of "Fresh Starts & Modest Changes"

Five years on, I think I probably feel even more strongly about this.

Partly because I've watched and read and heard the cyclical lamentations of folks who decided to use superficial totems (like new calendars) as an ad hoc coach and prime mover. And, partly because, in my capacity as a makebelieve productivity expert, I continue to see how self-defeating it is to pretend that past can ever be less than prologue--that we can each ignore yesterday's weather if we really wish hard enough for a sun-drenched day at the beach.

It simply doesn't work.

Companies that think they'll be Google for buying bagels. Writers who think they'll get published if they order a new pen. Obese people who think they'll become marathon runners if they pick up some new running shoes. And, regular old people with good hearts who continue to confuse new lives with new clothes.

Has this worked before? Can you look back on a proud legacy of successful New Year's resolutions that would suggest you're making serious progress by repeatedly making a list about fundamental life changes while slamming prosecco and wearing a pointy paper hat?

My bet is that most people who are seeing the kind of change and growth and improvement that sticks tend to avoid these sorts of dramatic, geometric attempts to leap blindly toward the mountain of perfection.

I'll go further and say that the repeated compulsion to resolve and resolve and resolve is actually a terrific marker that you're not really ready to change anything in a grownup and sustainable way. You probably just want another magic wand.

Otherwise you'd already be doing the things you've resolved to do. You'd already be living those changes. And, you'd already be seeing actual improvements rather than repeatedly making lists of all the ways you hope your annual hajj to the self-improvement genie will fix you.

Then, of course, we make things way worse by blaming everything on our pancakes.

Regarding "The First Pancake Problem"

Anyone who's ever made America's favorite round and flat breakfast food is familiar with the phenomenon of The First Pancake.

No matter how good a cook you are, and no matter how hard you try, the first pancake of the batch always sucks.

It comes out burnt or undercooked or weirdly shaped or just oddly inedible and aesthetically displeasing. Just ask your kids.

At least compared to your normal pancake--and definitely compared to the far superior second and subsequent pancakes that make the cut and get promoted to the pile destined for the breakfast table--the first one's always a disaster.

I'll leave it to the physicists and foodies in the gallery to develop a unified field theory on exactly why our pancake problem crops up with such unerring dependability. But I will share an orthogonal theory: you will be a way happier and more successful cook if you just accept that your first pancake is and always will be a universally flukey mess.

But, that shouldn't mean you never make another pancake.

So Loud. Then, So Quiet.

I offer all of this because today is January 7th, gang. And, for the past week, all over the web, legions of well-intentioned and seemingly strong-willed humans have been declaring their resolved intention to make this a year of more and better metaphorical pancakes.

And, like clockwork--usually around today or maybe tomorrow--a huge cohort of those cooks will begin to abandon their resolve and go back to thinking all their pancakes have to suck. Just because that first one failed.

And, as is the case every year, online and off, there won't be nearly as many breathless updates to properly bookend how poorly our annual ritual of aspirational change has fared. Which is instructive.

Not because new year's resolutions are a universally bad idea. And, not because Change is Bad. And, not because we should be embarrassed about occasionally falling short of our own (frequently unreasonable) aspirations.

I suspect we tout the resolution, but whisper the failure because we blame the cook. Or, worse, fingers point toward the pancake. Instead of just admitting that the resolution itself was simply unrealistic or fundamentally foreign.

And, that's a shame.

Remember, there's no "I" in "unreasonable"

Granted, I'm merely re-repeating a point I've struggled to make (to both others and myself) for years now. But, it will bear repeating every January in perpetuity.

Resist the urge to pin the fate of things you really care about to anything that's not truly yourself. The "yourself" who has a real life with complicated demands. The "yourself" who's going to face a hard slog trying to fold a new life out of a fresh calendar.

Calendars are just paper and staples. They can't make you care. And they can't help you spin around like Diana Prince, and instantly turn into Wonder Woman. Especially, if you're not already a hot and magical Amazon princess.

First, be reasonable. Don't set yourself up for failure by demanding things that you've never come close to achieving before. I realize this is antithetical to most self-improvement bullshit, but that's exactly the point. If you were already a viking, you wouldn't need to build a big boat. Start with where you are right now. Not with where you wish you'd been.

Also, accept that the first pancake will always suck. Hell, if you've never picked up a spatula before, be cool with the fact that your first hundred pancakes might suck. This is, as I've said, huge. Failure is the sound of beginning to suck a little less.

And, finally, also be clear about the sanity of the motivations underlying your expectations--step back to observe what's truly broken, derive a picture of incremental success that seems do-able, and really resolve to do whatever you can realistically do to actually get better. Rather than "something something I suddenly become all different."

At this point, you have logistical options for both execution and troubleshooting:

• Make a modest plan that you can envision actually doing without upending your real life;
• Build more sturdy scaffolding for sticking with whatever plan you've chosen;
• Make a practice of learning to not mind the duds--including those messed-up first pancakes;
• Or--seriously?--just accept that you never really cared that much about making breakfast in the first place. Care is not optional.

Otherwise, really, you'd never need to resolve to do anything. You'd already just be cooking a lot. Instead of being all mad and depressed about not cooking.

But, please. All I really ask of you. Don't blame the pancake. It's not really the pancake's fault.

Like me, the pancake just wants you to be happy. This and every other new year.

The following article, BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation, was first published on 100PercentFedUp.com.

Yesterday, Senator Marsha Blackburn (R-TN), along with Senator Martha McSally (R-AZ) introduced the Stop COVID Act, giving Americans the ability to sue Communist China for the damage they’ve inflicted on our nation. Senator Blackburn appeared on Fox News with host Judge Jeanine where she explained the act to Jeanine Pirro. Blackburn told the Fox News […]

Continue reading: BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation ...

After being pulled over for what started as a traffic violation, two Windsor men were arrested and face multiple drug, property, and weapon related charges.

Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early, and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the nonphotopic or photopic visual cycles for mediating vision in bright light.

The newly published Inclusive Top 50 UK Employers showcases leading organizations working across all strands of diversity.

Invitation Only Research Event

Event participants

Ambassador Lee Feinstein, Founding Dean, School of Global & International Studies, Indiana University
Xenia Wickett, Project Director, US; Dean, The Queen Elizabeth II Academy, Chatham House
Paul Arkwright, Director, Multilateral Policy, Foreign & Commonwealth Office
Dr Patricia Lewis, Research Director, International Security Programme, Chatham House
Jonathan Prentice, Director, London Office & Senior Adviser for European Advocacy, International Crisis Group
Sir John Holmes, Director, The Ditchley Foundation

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research