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Picture time! NCC says ‘feel free’ to snap a photo of the tulips

As the tulips begin to bloom across Ottawa, the National Capital Commission now says you can stop and take a photo of the colourful flowers.





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‘Bloodshot’ works, if only for the cinematic universe it has the potential to create

Vin Diesel stars as Bloodshot as Valiant Comics finally makes it to the big screen.




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The world is getting hotter. Can temperature-controlled clothing provide some relief?

Sony has introduced a new product called the Reon Pocket, which operates like a mobile air conditioner that fits inside clothing.




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At this Chinese hotel, the bellhops have been replaced by talking robots

Robots are showing up in more and more hotels all over the world. A Washington Post reporter's video captures what it's like to interact with one.




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Four long shots for Saturday’s Breeders’ Cup races

Favorites have won 99 of 318 races (31 percent) in the Breeders’ Cup.




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The Polaris Slingshot is a car-motorcycle mashup that costs $33,000 and can do 0-60 mph in 5 seconds — on 3 wheels.

  • I tested a roughly $33,000 Polaris Slingshot R, a three-wheeled "autocycle."
  • The three-wheeler category includes vehicles from Can-Am and Harley-Davidson, offering a motorcycle experience in a less demanding package.
  • My Slingshot R had a new, Polaris-developed, 203-horsepower engine and an automatic transmission.
  • In all but three US states, no motorcycle license is required to operate the Slingshot (New York, Massachusetts, and Alaska continue to require the motorcycle certification).
  • The Slingshot is insanely fun, with a modest learning curve — it's a great alternative to a two-wheeler, although the price is definitely steep for the Slingshot R.
  • Visit Business Insider's homepage for more stories.

Motorcycles are cool, but they aren't for everybody. Fortunately, there are some alternatives out there that offer an equally compelling, open-air experience.

One of the most popular is the the Polaris Slingshot, manufactured by the Minnesota-based powersports company. Until recently, Slingshots were available only with manual transmissions and GM-sourced engines, but for 2020, Polaris has updated the autocycle with an in-house motor and an automatic.

The automatic transmission in particular really broadens the Slingshot's potential. So I was excited to sample the machine, which I first saw about five years ago.

Polaris was kind enough to loan me a tester for a few weeks. Here's how it went:

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The Polaris Slingshot is a three-wheeled autocycle/motorcycle that Polaris industries has produced since 2014. My 2020 Slingshot R tester cost about $33,000 and was outfitted in a menacing red-and-black paint job.

The cheapest Slingshot is about $20,000.



This wasn't my first crack at a Slingshot. Polaris brought the vehicle to Insider's New York offices when the vehicle first launched.



And I generally have a gander at the Slingshot when I visit the annual New York motorcycle show.



The Slingshot is classified as either a motorcycle or an autocycle, depending on which state it's being operated in.



Yep, it looks like the Batmobile. Or Batcycle. Hard to avoid feeling like a superhero when you're behind the wheel. In all but three US states, no motorcycle license is required to drive the Slingshot. In New Jersey, you are required to wear a helmet.

Up front, you have 18-inch forged aluminum wheels, with an 20-incher at the back. The brakes have two-piece composite rotors.



Permanent open-air motoring isn't for everybody. Polaris does sell and older model, the Grand Touring, which has a cockpit canopy. The Polaris R has a waterproof interior and drain holes in the floorboards, should you get caught in bad weather.



My tester was the top-level "R" trim, complete with dual roll bars for drier and passenger.



Let's talk fender fairings! The Slingshot's are dramatic and large — I was reminded of Chevy Corvettes while driving this thing. Like a motorcycle, there's no rear-view mirror, so you have to adjust slightly to using the sideviews.



There's a new engine under the hood. Previously, Polaris used a 2.4-liter, four-cylinder GM-sourced Ecotech motor, making up to 175 horsepower. But my R had a ProStar four, also at 2.4-liters, cranking out 203 horsepower with a five-speed automatic transmission (a manual remains available). It's an in-house engine that was impressive in action.

The top speed is limited at 125 mph, and the 0-60mph run, according to Polaris and confirmed by yours truly, is about five seconds.

The four-banger redlines at 8,500 rpm and even with the automatic transmission does a pretty fair imitation of proper motorcycle acceleration. The auto is a tad crunchy, but in this context, that's a plus. It keeps you aware of what the engine is doing.



The rear wheel — fat and wide — is yoked to the motor and transmission with a belt drive. The suspension is surprisingly compliant, but you do have to be mindful of bumps, potholes, and manhole covers if you want to preserve you lower spine.



Polaris says the interior has been upgraded for 2020. No one would call it premium, but for a vehicle like this, it's rather comfortable.



The steering wheel is leather-wrapped, multifunctioned, and flat-bottomed to make getting into and out of the driver's seat easier.



The instrument cluster is a basic analog affair with a central digital display. The red button to on the right steering-wheel spoke allows you to switch between Comfort and Slingshot modes (the latter being the high-performance option).



The bucket seats are waterproof and extremely well-bolstered, with three-point seat belts.



The Slingshot's tubular frame is apparent in the doorless frame.



Not really much cargo capacity here, although I did use the Slingshot for a grocery-store run and quick jaunt to Target to buy a basketball.



There is a place to stow a smartphone, located just above the push-button gear selector.



The Slingshot also has push-button start-stop.



The glove compartment is the only other storage available ...



... And it's actually pretty roomy. One could stash a rain jacket in there, for example.



The RideCommand infotainment system is basic — but good! On a vehicle such as this, I wasn't expecting much, but the audio setup sounded decent, the screen was responsive, and Bluetooth and USB connectivity was on-par with what you'd find in any modern automobile.



There's even GPS navigation, which can display a map and provide turn-by-turn guidance.



The ride-mode selector is doubled in the infotainment system.



So what's the verdict?

I love three-wheelers. They aren't as cool as two-wheeled motorbikes, but they provide easy access to open-air motoring, and the driving/riding experience is much more engaging than what you find in convertible automobiles.

For anybody who dislikes the impracticality of motorcycles but wants to partake of the open-road lifestyle, machines like the Slingshot (the Can-Am Spyder and the Harley-Davidson Freewheeler, to name two) are ideal.

Not for nothing, they also offer aging riders a chance to yank their helmets and biker jackets out of storage to pursue moderately safer riding. With the Slingshot, gearing-up isn't necessary.

The trade-off, of course, is price. The Slingshot R that I tested costs more than an entry-level car or SUV. So, an expensive plaything. But there's nothing wrong with that. Everybody needs a hobby.

No doubt about it, the Slingshot captures attention. I lost count of how many little kids a stopped in their tracks as I tooled around the Jersey suburbs. The last vehicle that provoked such astonishment was the Lamborghini Huracán Performante. If you become a Slingshotter, prepare to be pointed at and asked for photo-ops.

Driving-wise, the Slingshot scratches an itch: on the road, the experience is unexpurgated — you don't have to be constantly vigilant, as you would on a bike, but you do need to remain aware. Highway trips are demanding. And noisy. And exhilarating. The Slingshot R is also fast and torque-y and the power goes to the single back wheel, so the while the two-wheeled front is stable, the back end can get pretty wiggly, especially in Slingshot mode, if you stomp the throttle.

I had iffy springtime Northeast weather to contend with, so I took the Slingshot out only on warm and sunny days; the rest of the time, I parked it in my garage. But the vehicle can handle being rained on, and one could also buy a cover to protect it from the elements. To be honest, however, I think it's a better choice in warm, dry climates. 

The performance is aggressively go-kart-y. This thing will make you a better drive, thanks to its point-and-shoot steering, crisp suspension, and easy access to power. It's insanely fun on curves and into corners. But it's also worthy of short road trips. In fact, the relative comfort was a shocker: I took the Slingshot out for a few hours one day and suffered no ill-effects to my lower back.

Drawback? The design is thoroughly sporty, so if you don't go in for that, the Slingshot might not be your bag. It isn't a throwback, nor is it at all steam-punky. 

It also isn't a motorcycle, in that there aren't any handlebars, you don't throw a leg, and the single wheel takes up the rear. 

But the Slingshot is a absolute blast, and if you're a weekend warrior who wants to carve up a canyon or a country road without having the grapple with a motorcycle's demands — and you don't mind dropping some dollars — the Slingshot is perfect.






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Stephen Miller marries Katie Waldman at the Trump International Hotel — with president in attendance

The president stopped by the event for Miller, a senior adviser, and Waldman, press secretary to Vice President Pence, after attending the Daytona 500.




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Kids and Screenshots

If you have kids with mobile devices, create a central home charging station in a place like your bedroom. Before the kids go to bed at night, have them put their mobile devices there so they are not tempted to play with them when they should be sleeping.




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5 Ways A European Hotel Barge Cruise Is Better Than A River Cruise

Is a hotel barge cruise better than a river cruise in Europe? I explore 5 times, and types of travellers, where a European barge hotel cruise is likely to be the best way to cruise through Europe. River cruising in Europe has become very popular, but less travellers know there is an alternative way to cruise the European Waterways - hotel barges that cruise the canals and rivers of Europe. Discover if they are a better option for your European vacation

Note: I travelled as a guest of CroisiEurope on a 6-night French cruise on their Deborah hotel barge along the Yonne and Seine from Sens to Paris. The cost of the cabin would have been £2043 / $2500 per person sharing. CroisiEurope had no input on the content or opinions expressed in this video.

** Buy my Cruise T-shirts: http://bit.ly/TFTStore
** USA cruisers get great cruise deals CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise
** UK Cruisers get great cruise deals with CRUISE.CO.UK: http://bit.ly/BookCruiseUK

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




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How to Setup & Use iCloud Photos on Mac

Want to use iCloud Photos on Mac? In its simplest form iCloud Photos is a sync service that makes sure your iPhone, iPad, Apple Watch, Apple TV, and Mac all have every photo you’ve taken, all ready at a moment’s notice. That means you can access the photos from any other device with the feature ... Read More




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News24.com | US rocked by another unarmed black man being shot dead

Politicians, celebrities and people speaking out on social media are angrily demanding the arrest of two white men in the shooting death of an unarmed black jogger in Georgia.




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Hotfile sues Warner Bros., claims wrongful takedowns

Warner Bros. systematically abused an automated takedown system provided by Hotfile, the file host claims in a countersuit against the studio. The claims made by Hotfile include information on the behind-the-scenes actions taken by Hollywood to enforce its rights against file sharing on cloud file hosts. Continue reading on NewTeeVee.


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A Note About the State of My Photography Tours and Workshops

This is a quick update about how things are going to be working with my travel photography tours during this time of crisis.  Obviously, with international travel nearly impossible right now, some changes needed to happen, and some adjustments are going to need to continue over the next couple months. Below, I chat quickly about […]

The post A Note About the State of My Photography Tours and Workshops appeared first on Brendan van Son Photography.



  • Travel Photography Blog

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Cancelling/Postponing Photography Trips

This week has been a tough one.  It has just become more and more clear that the global travel situation isn’t going to clear up until at least early in the fall.  So while we’re still very hopeful that our Namibia trips starting in September will still happen, we’ve sadly had to cancel or postpone […]

The post Cancelling/Postponing Photography Trips appeared first on Brendan van Son Photography.




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AT#45 - Travel Photography (interview with Chris Marquardt)

Travel Photography (interview with Chris Marquardt)




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AT#88 - Travel Photography tips

Travel Photography tips




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AT#215 - Travel Photography

The Amateur Traveler talks to photographer Ralph Velasco about tips to keep in mind when you are taking pictures on your travels. We talk about:

    * telling a story
    * depth of field
    * giving your self assignments
    * giving a sense of scale
    * adding a human touch
    * reflections
    * avoiding the crowds
    * embracing the weather
    * seeking the unique picture
    * capturing the essence of a place




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AT#255 - Photo Tour of Egypt

Chris, the Amateur Traveler himself, talks about the recent Ralph Velasco / Amateur Traveler Photo Tour of Egypt which was a guided tour of Egypt run by Cosmos. The tour started in Cairo with the Pyramids and the Sphinx, the Egyptian museum, old mosques, churches and synagogues before moving on to the port city of Alexandria. After seeing the historic sites in Alexandria like Pompey’s Column and the Catacombs we continued on to the site of the battle of El Alamein and then to Marsa Matruh in the Northwest corner of Egypt on the Mediterranean. We continued back to Cairo with a stop at a Coptic Monastery and then flew to Aswan to tour Upper Egypt. We saw temples from the Greek period and the New Kingdom from Aswan to Luxor including the Temple to Ramses at Abu Symbel, the temple to Isis, the temple of Etfu, the Luxor temple and the great temple of Karnak. We also visited the Valley of the Kings and a Nubian village. Along the way we shopped and photographed.




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AT#301 - Travel to Chihuahua, Mexico with Photographer Ralph Velasco

Chihuahua is also known for the beautiful Cooper Canyon which is best seen from the train that transverses it. Copper Canyon is a popular tourist destination with Mexicans. Copper Canyon is larger and portions are deeper than the Grande Canyon.




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Take Control of Your Digital Photos

Digital cameras make it easy to take way too many pictures. Need help sorting, organizing, storing, and managing them? We've got a great book for you—and Interesting Thing of the Day readers can save 30% on it.



  • Book of the Week

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Jupiter looks pretty angry in "lucky" infrared shot

It took hundreds of exposures and a complex method of removing occlusions, but this "lucky" shot is the result: a depiction of the hot regions lurking under Jupiter's uppermost clouds.

The picture was captured in infared by the Gemini North Telescope in Hawaii, and is one of the sharpest observations of the planet ever made from the ground. To achieve the resolution, scientists used a technique called "lucky imaging" which scrubs out the blurring effect of looking through Earth's turbulent atmosphere. This method involves acquiring multiple exposures of the target and only keeping those segments of an image where that turbulence is at a minimum.

Read the rest




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Photo Gallery: 75th Anniversary of VE Day

Friday, May 8, 2020, marks the 75 anniversary of VE Day.




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Photos Of Kim Jong Un Spark Conspiracy Theories About A Body Double…You Be The Judge

The following article, Photos Of Kim Jong Un Spark Conspiracy Theories About A Body Double…You Be The Judge, was first published on 100PercentFedUp.com.

For several weeks rumors of the North Korean dictator’s sickness and ultimately, his death, have been making their rounds in the media. North Korea’s state-run media released photos of  Kim Jong Un that were allegedly taken on May 1, at the opening of a fertilizer factory in Sunchon, N. Korea. Twitter users who’ve studied the images are […]

Continue reading: Photos Of Kim Jong Un Spark Conspiracy Theories About A Body Double…You Be The Judge ...




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BREAKING: 43-Yr-Old Father Of 9, Dollar Store Sec Guard, Shot DEAD While Allegedly Trying To Enforce MI Gov Whitmer’s Face Covering Exec Order

The following article, BREAKING: 43-Yr-Old Father Of 9, Dollar Store Sec Guard, Shot DEAD While Allegedly Trying To Enforce MI Gov Whitmer’s Face Covering Exec Order, was first published on 100PercentFedUp.com.

Will the mainstream media report about the senseless death of a 43-year-old father of nine, who would have been alive today if it were not for VP wannabe, Gretchen Whitmer's executive order that forced him to respond to a customer not wearing a face mask? 

Continue reading: BREAKING: 43-Yr-Old Father Of 9, Dollar Store Sec Guard, Shot DEAD While Allegedly Trying To Enforce MI Gov Whitmer’s Face Covering Exec Order ...




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'Quaranscream': Wine spritzer company opens Mother's Day venting hotline

A beverage company in the U.S. is inviting moms to let out a ‘quaranscream’ this Mother’s Day on a designated ‘zero-judgement venting hotline’ for a chance to win its wine spritzers.




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Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes [Plant Biology]

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.




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Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision [Molecular Bases of Disease]

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.




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The Proteome of the Mouse Photoreceptor Sensory Cilium Complex

Qin Liu
Aug 1, 2007; 6:1299-1317
Research




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Interpretation of Shotgun Proteomic Data: The Protein Inference Problem

Alexey I. Nesvizhskii
Oct 1, 2005; 4:1419-1440
Tutorial




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Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics

William M. Old
Oct 1, 2005; 4:1487-1502
Research




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G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction]

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis.




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Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes [Plant Biology]

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.




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A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
Articles




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G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction]

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis.




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Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research]

Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal.

In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested.

Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation.

Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient.





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Finding Fake Photos

Actually, they weren.t caught together at all their images were put together with software. The shadows cast by the stars. faces give it away: The sun is coming from two different directions on the same beach! More elaborate digital doctoring is detected with mathematics. Calculus, linear algebra, and statistics are especially useful in determining when a portion of one image has been copied to another or when part of an image has been replaced. Tampering with an image leaves statistical traces in the file. For example, if a person is removed from an image and replaced with part of the background, then two different parts of the resulting file will be identical. The difficulty with exposing this type of alteration is that both the location of the replacement and its size are unknown beforehand. One successful algorithm finds these repetitions by first sorting small regions according to their digital color similarity, and then moving to larger regions that contain similar small ones. The algorithm.s designer, a leading digital forensics expert, admits that image alterers generally stay a step ahead of detectors, but observes that forensic advances have made it much harder for them to escape notice. He adds that to catch fakers, At the end of the day you need math.(1) For More Information: Can Digital Photos be Trusted?, Steve Casimiro, Popular Science, October 2005. _______ 1 It May Look Authentic; Here.s How to Tell It Isn't, Nicholas Wade, The New York Times, January 24, 2006.




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The photo gallery for the COP-MOP 6 is now available




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CBD Communiqué: Young Talent Recognised in Global Photography Competition.




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CBD News: Statement by Mr. Braulio Ferreira de Souza Dias, CBD Executive Secretary, on the occasion of the International Day for Biological Diversity, 22 May 2012, Hotel GRT, Chennai, India




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CBD News: The ecologically or biologically significant marine areas (EBSA) booklet series provide snapshot summaries of the pages upon pages of data compiled by participating experts, to provide an inspiring overview of some of the most ecologically or bi




hot

G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction]

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis.




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Carbon footprint hotspots: Mapping China's export-driven emissions

(University of Michigan) The coronavirus pandemic has highlighted just how reliant the United States and other countries are on Chinese manufacturing, with widespread shortages of protective medical gear produced there.




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Arizona State University scientists rewire photosynthesis to fuel our future

(Arizona State University) Hydrogen is an essential commodity with over 60 million tons produced globally every year. However over 95 percent of it is made by steam reformation of fossil fuels, a process that is energy intensive and produces carbon dioxide. If we could replace even a part of that with algal biohydrogen that is made via light and water, it would have a substantial impact.




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Seafloor currents may direct microplastics to biodiversity hotspots of the deep

(American Association for the Advancement of Science) Microplastic particles entering the sea surface were thought to settle to the seafloor directly below them, but now, a new study reveals that slow-moving currents near the bottom of the ocean direct the flow of plastics, creating microplastic hotpots in sediments of the deep sea.




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Could hotel service robots help the hospitality industry after COVID-19?

(University of Surrey) A new research study, investigating how service robots in hotels could help redefine leadership and boost the hospitality industry, has taken on new significance in the light of the seismic impact of the Covid-19 outbreak on tourism and business travel. The study by academics at The University of Surrey and MODUL University Vienna focuses on how HR experts perceive service robots and their impact on leadership and HR management in the hotel industry.




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MaxQuant software for ion mobility enhanced shotgun proteomics

Nikita Prianichnikov
Mar 10, 2020; 0:TIR119.001720v1-mcp.TIR119.001720
Technological Innovation and Resources




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Label-free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-guided Surgery by Photoacoustic Imaging

Objectives: The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of study is to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma in a very early stage and perform tumor resection by intraoperative photoacoustic image-guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a B16 melanoma hepatic metastasis mouse model (n = 10) was established to study the development of micrometastases in vivo. Next, the hepatic metastasis mice models were imaged by scalable PAI instrument, ultrasound, 9.4 T high-resolution magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), and bioluminescence imaging. Photoacoustic images acquired with optical wavelengths spanning from 680 to 850 nm were spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in the signal-to-background ratios among different modalities were determined with the two-tailed paired t test. The diagnosis results were assessed with histologic examinations. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify tumor boundary. In vivo metastatic melanoma removal in surgery was precisely guided by the portable PAI system. Results: PAI achieved as small as ~400 µm hepatic melanoma detection at a depth up to 7 mm in vivo, which could early detect small melanoma compared with ultrasound and MRI in mouse models. The signal ratio of tumor-to-liver acquired with PAI in micrometastases at 8 days (4.2 ± 0.2, n = 6) and 14 days (9.2 ± 0.4, n = 5) were significantly higher than those obtained with PET/CT (1.8 ± 0.1, n = 5 and 4.5 ± 0.2, n = 5, P <0.001 for both). Functional PAI provided dynamic oxygen saturation changes during tumor growth. The limit of detection was measured to be approximately 219 cells per microliter in vitro. We successfully performed intraoperative photoacoustic image-guided surgery in vivo using the rapid portable PAI system. Conclusion: Our findings offer a rapid and effective tool to noninvasively detect micrometastases and guide intraoperative resection as a complementary clinical imaging application.




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PET/CT imaging with a 18F-labeled galactodendritic unit in a galectin-1 overexpressing orthotopic bladder cancer model

Galectins are carbohydrate-binding proteins overexpressed in bladder cancer (BCa) cells. Dendritic galactose moieties have a high affinity for galectin-expressing tumor cells. We radiolabeled a dendritic galactose carbohydrate with fluorine-18 – 18F-labeled galactodendritic unit 4 – and examined its potential in imaging urothelial malignancies. Methods: The 18F-labeled 1st generation galactodendritic unit 4 was obtained from its tosylate precursor. We conducted in vivo studies in galectin-expressing UMUC3 orthotopic BCa model to determine the ability of 18F-labeled galactodendritic unit 4 to image BCa. Results: Intravesical administration of 18F-labeled galactodendritic unit 4 allowed specific accumulation of the carbohydrate radiotracer in galectin-1 overexpressing UMUC3 orthotopic tumors when imaged with PET. The 18F-labeled galactodendritic unit 4 was not found to accumulate in non-tumor murine bladders. Conclusion: The 18F-labeled galactodendritic unit 4 and similar analogs may be clinically relevant and exploitable for PET imaging of galectin-1 overexpressing bladder tumors.