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Ribosome Unties the Messenger-RNA Gordian Knot

first_imgCells needing to translate their DNA into proteins have a problem.  The messenger RNAs, the molecules that carry the genetic code from the nucleus to the translating machine called the ribosome, get tied up in knots.  How does the ribosome untie them before they can begin translating?  Takyar et al., writing in Cell,1 explored this problem and found that the ribosome has a novel solution.    If you have seen the film Unlocking the Mystery of Life, you watched a messenger RNA molecule, nice and straight, exit the nuclear pore complex and neatly enter the ribosome, like a man reclining in a barber chair waiting to get a haircut.  Unfortunately, things are not so simple.  Because of chemical affinities between the bases of the RNA molecule, the bases attract other bases (base-pairing) or else fold over on themselves, forming amorphous lumps (secondary structure).  Untangling this mess would be like straightening out a chain of several hundred magnets that has clumped together.    The untangling problem is not unique to messenger RNA (mRNA).  DNA in the nucleus also has to be unwound.  Each of the processes of “replication, DNA repair, recombination, transcription, pre-mRNA splicing, and translation” have their own specialized enzymes, called helicases, that latch onto the nucleic acids and work their way down the helix, unwinding them for whatever subsequent operation is necessary.  Until now, though, no helicase was found associated with the ribosome.  It turns out the helicase activity is built-in.    The ribosome has an entry tunnel and exit tunnel.  As the mRNA strand enters, specialized proteins named S3, S4 and S5 are precisely placed to form a ring around the mRNA helix.  They grab the phosphate groups on the side chains and separate the base pairs.2  There’s only room in the tunnel for a single strand.  As the interior of the ribosome pulls the mRNA through, this entry-tunnel helicase, built into the walls of the tunnel, effectively “melts” the double strands, sending in a clean single strand for the translation machinery to work on.  And how does the ribosome pull it in? In their studies of ratcheting of the two ribosomal subunits between the pre- and posttranslocation states, Frank and Agrawal (2000) observed a reciprocal expansion and contraction in the diameter of the upstream and downstream tunnels, suggesting that these two features may alternately grab and release the mRNA during translocation of mRNA.  This dynamic behavior in the downstream tunnel could also be related to its helicase function.  (Emphasis added in all quotes.)The action seems analogous to those old Dymo labelmakers people used to use for labeling household items.  You remember: as your hand clicked the machine, the tape came in one tunnel and out another.  In the case of the ribosome, the entry and exit tunnels alternately expand and contract, forcing the mRNA molecule to ratchet through the system.  The ratchet prevents backward motion and also is delicate enough to prevent breakage of the single strand during the unwinding process.    The placement of S3, S4 and S5 in the tunnel is critical.  The researchers found that when they were mutated, the helicase activity stopped.  Because it latches onto the phosphates, which are universal to RNA molecules, they can unwind any strand, regardless of the sequence of base pairs.    The authors do not speculate on how this helicase system, which is unique to the ribosome, evolved.  They only note that if it did, the unwinding puzzle needed to be solved by the very first living cell:The inescapable presence of secondary structure within mRNA coding sequences must have been one of the first problems encountered in the transition from an RNA world to a protein world and may have resulted in coupling of ribosomal helicase activity with the fundamental mechanics of translocation.How this was accomplished by a sequence of random changes, they do not explain.1Takyar et al., “mRNA Helicase Activity of the Ribosome,” Cell, Vol 120, 49-58, 14 January 2005.2It was not clear to the authors whether the helicase pulls the bases apart with the expenditure of energy.  It may be that the helicase can take advantage of spontaneous separation.  Base pairs tend to “breathe” as their weak hydrogen bonds stretch.  The helicase may be able to latch onto the nucleotide during its spontaneous separation, as if saying “Aha!  Gotcha!” and prevent the hydrogen bond from re-forming.Again, we see an elaborate system, with only a wave of the Darwinian hand to explain it.  It is a cardinal sin of evolutionists that they merely assume evolution can solve any problem the realities of chemistry, physics and the environment throw at life.  They invoke hypothetical lucky mutations, never observed, that somehow appeared at the right time and place to produce irreducibly complex structures like ribosome helicase.    Take off the funky Darwin glasses and what do you see?  Evidence of exquisite, effective design.  The authors take note that this helicase activity is very efficient and works rapidly: “The ability of the ribosome to unwind a long, highly stable helix shows that it is a highly processive helicase, capable of successive disruption of many base pairs without dissociation from the mRNA.”  Materialists decry miracles, yet they want us to believe nature solved this problem so exquisitely all by itself.  Come, let us reason together.(Visited 9 times, 1 visits today)FacebookTwitterPinterestSave分享0last_img read more


Ohio Ag Weather and Forecast December 5, 2018

first_imgShare Facebook Twitter Google + LinkedIn Pinterest Clouds and a bit of light precipitation hangs around this morning over Ohio, with lake effect snow potential still off an on today in NE Ohio. However,  we should see some improvement through the day. Clouds will break up a bit toward midday and we should see some sunshine trying to work through from time to time in the afternoon. The improvement still looks like somewhat of a short-term development. A minor disturbance drifts across the state tomorrow, bringing minor snows. The action comes into western Ohio around midday and spreads east before drifting south through the evening and overnight. Moisture is not impressive with only a few hundredths to a tenth of liquid equivalent, but that could yield a coating to an inch of light snow with 60% coverage. The map at right shows the Thursday action.Dry weather is back on Friday and holds all the way through next Thursday morning. A strong system is passing by to the south of the Ohio river this weekend. That will bring a reinforcing shot of cold air that comes into the state over the weekend, taking temps well below normal. This should help to firm up ground conditions a bit. It will be the longest dry window we have seen statewide in quite a while.Toward the end of the 10-day period we see moisture returning. South winds will promote some warming over the state, and light rains move in for next Thursday midday through Thursday night. Rain totals will be from .1” to .5” with 70% coverage. However, a bigger watch point is the following Friday. Some models are suggesting a stronger second bubble of moisture up on to the area from the southwest. If this comes together, it would trigger rains of .25”-1” over the state, with the focus on the southwest quadrant of Ohio. We want to see a little more data and information pointing this way before making big changes to the forecast, though.In the extended period, we are pushing our main system back about 24 hours. We still look for good rains to fall on the 17th and that moisture ends as snow on the 18th. Moisture totals are not as impressive as our earlier look, but we are keeping .25”-1” rain potential in, and then just some minor snows. A second system is trying to develop closer to the 20th, but would be all snow, as it stands right now.last_img read more


What are the scary ripple effects of autonomous mobility?

first_imgBreak the Mold with Real-World Logistics AI and… By 2040, we think fifth-level, autonomy-enabled mobility will be available as a service for the majority of the transportation needs of urban consumers. In other words, 70% of the urban population wouldn’t need to own cars because they would be available on-demand through their favorite app. Although several power players like General Motors and Ford are promising fully autonomous cars sooner, there are many technological and large-scale regulatory and consumer sentiment issues with autonomous cars that would need to be addressed before they could fulfill our transportation needs. See also: Report predicts 95% of cars will be autonomous by 2030But imagine the world in 2040, when most of the population doesn’t need cars. Everything from shopping to commuting to long distance road trips will be addressed by fully autonomous vehicles that you can summon with the push of a button. Rethinking today’s products and services in the 2040 worldOnce you accept that basic premise, it is surprising to see how so many of our current products and services do not fit well with the world of the fully autonomous car. When we shift from complete ownership to an on-demand leasing model, automotive OEMs and their supply chains (Tier 1 and Tier 2) will be the first ones affected. Several of them are thinking of strategies to grapple with this eventual reality, but this is just the tip of the iceberg. A significant number of multibillion dollar companies operate around consumers owning at least one to two cars per family. All these products and services will either become obsolete or have to be fundamentally rethought. 15 minutes for an insurance product we don’t need? Let us start with the way we buy cars — at dealerships. Once consumers stop buying cars, there is no need for dealership networks. They are merely a distribution channel that will be replaced by an app that we use to hail our cars. Then, there’s insurance; we get insurance as soon as we buy a car. Because we will no longer own cars, there is no need to spend 15 minutes to save on car insurance. Accidents because of systemic failures like poor connectivity or algorithmic edge cases are inevitable, but the massive reduction in the frequency of accidents coupled with insurance being bundled into the mobility service will result in an enormous reduction in revenue for the insurance industry. Car loans, which finance our car ownership, will also be out. In the 2040 world, mobility service providers will end up owning most of the cars. Even if you assume one or two ride hailing apps will dominate the market, there are economies of scale in owning and operating large autonomous car networks. As a result, we believe the ultimate owner of the cars will be large businesses, not individual car owners who would lease their cars on ride sharing platforms. These large fleet owners would have a low cost of capital with which to finance their vehicle purchases. Through both a massive reduction in the number of cars and the APR they can charge for each car loan, auto loan providers will see a huge downsizing of their market. First stop on the road to oblivion: gas stationsOnce we buy our cars, we spend a lot of money on it. Let us think about these products and their relevance in the 2040 world.  The first and most obvious car-related expense is gas. In a world where we have autonomous car fleets operating, we don’t need as many gas stations. A few large gas stations far away from high-density areas and perhaps operated, once again, by large fleet owners should suffice. These cars would essentially act like public transportation vehicles, which are refueled at the end of each day at a central location. A fewer number of miles traveled because we will be using ride sharing services, with more fuel efficient cars will certainly be a cause for concern for oil companies. Parking is another common expense with a poor consumer experience. The omnipotence of autonomous ride-sharing cars will lead us to have fewer parking lots away from high-density areas where mobility service providers can park their automotive fleets when demand is low. Close to half of our urban areas are dedicated to parking, and therefore, a massive reduction in parking lots will be a boon to our cities. Every big technological change has massive unforeseeable consequences At conception, the Internet was a platform only for email. But its unintended consequences ended up creating companies like Amazon, Google, and Facebook, which have changed the way we buy and consume media. In the same vein, we believe autonomous mobility will fundamentally change the way we live in our cities. So much of our urban real estate is tied to car ownership model of today: parking lots, gas stations, dealerships. No one can foresee the new products or services that could emerge from such surplus real estate becoming available or the effects it will have on our housing markets. Will people live much farther from cities because commuting in an autonomous car could be productive, or would urban housing become cheaper because we don’t need parking lots anymore? And as for my personal favorite unintended consequence, short distance flights — would we rather take a flight from San Francisco to Los Angeles or would we prefer to get there in swankier-than-business-class autonomous vehicles that come with plush beds and Netflix? I am extremely confident that there are many more positive, albeit unintended, consequences of autonomous cars that will emerge en-route to 2040. So why is this scary? The 2040 world of autonomous mobility is scary because so many of today’s products and services would have to radically evolve to stay relevant. And it is not just the automotive OEMs that are in trouble — auto insurance companies, car loan providers, oil and gas companies, car dealerships, parking lot owners, and auto parts suppliers and stores are all on the chopping block. Just this foreseeable disruption alone is worth $2 trillion in terms of products and services we consume today. If these companies are affected, it will set off a chain reaction of problems for suppliers, which will trigger panic. See also: Will elderly and disabled gain most from driverless cars?This $2 trillion will be reshuffled and distributed to consumers, new companies and incumbents. And that is scary. Some of the best incumbent players in all the industries highlighted above are already thinking ahead to prepare and adapt to new reality. But many others will likely not survive this disruption. That’s scary, too. Preparing for the 2040 future now by partnering with startups and augmenting your organization with change makers that can imagine the future well before it has arrived is essential if incumbent companies want to survive in this changing landscape. But for the startup founders and venture capitalists involved in the industry, the evolution of autonomous cars is an enormous and exciting opportunity that has the potential to create multiple $1 billion technology companies. Uber and Lyft are just the beginning. The author is a rogue scientist turned venture capitalist focusing on investments in Data, Automation Artificial Intelligence (A.I.), and frontier technologies at Draper Nexus. He co-led the investment in Nauto, an A.I. enabled dashboard camera that provides driver safety and road scene analytics to automotive OEMs, commercial fleets, and insurance companies. Through learnings from this investment, he has further built out the firm’s investment thesis in autonomous mobility. Tags:#autonomous vehicles#driverless cars#industry 4.0#Internet of Things#IoT#Self-Driving IT Trends of the Future That Are Worth Paying A… For Self-Driving Systems, Infrastructure and In…center_img Deepak Jagannathan 5 Ways IoT can Help to Reduce Automatic Vehicle… Related Posts last_img read more