Cell Backup Systems Challenge Evolution, Show Design Principles

first_imgHas an intelligent design paper been published in the Proceedings of the National Academy of Sciences?1  Read the abstract and decide whether this research supports Darwinism or design:Functional redundancies, generated by gene duplications, are highly widespread throughout all known genomes.  One consequence of these redundancies is a tremendous increase to the robustness of organisms to mutations and other stresses.  Yet, this very robustness also renders redundancy evolutionarily unstable, and it is, thus, predicted to have only a transient lifetime.  In contrast, numerous reports describe instances of functional overlaps that have been conserved throughout extended evolutionary periods.  More interestingly, many such backed-up genes were shown to be transcriptionally responsive to the intactness of their redundant partner and are up-regulated if the latter is mutationally inactivated.  By manual inspection of the literature, we have compiled a list of such “responsive backup circuits” in a diverse list of species.  Reviewing these responsive backup circuits, we extract recurring principles characterizing their regulation.  We then apply modeling approaches to explore further their dynamic properties.  Our results demonstrate that responsive backup circuits may function as ideal devices for filtering nongenetic noise from transcriptional pathways and obtaining regulatory precision.  We thus challenge the view that such redundancies are simply leftovers of ancient duplications and suggest they are an additional component to the sophisticated machinery of cellular regulation.  In this respect, we suggest that compensation for gene loss is merely a side effect of sophisticated design principles using functional redundancy.The three authors, all from the Weizmann Institute in Rehovot, Israel, speak freely of the evolution of this phenomenon in their paper; they also, interestingly, refer to design and design principles just as often:In particular, we suggest the existence of regulatory designs that exploit redundancy to achieve functionalities such as control of noise in gene expression or extreme flexibility in gene regulation.  In this respect, we suggest that compensation for gene loss is merely a side effect of sophisticated design principles using functional redundancy.    Clues for regulatory designs controlling redundancy were obtained first in a recent study…They call these cases of functional redundancy responsive backup circuits (RBCs).  Interestingly, they found some cases where one RBC is regulated by another RBC.  Though often the two backup copies were differently regulated, they could become coregulated under certain environmental conditions.  The team also found that some of these functionally redundant genes are found all the way from yeast to mammals; this is sometimes called “evolutionary conservation” but actually describes stasis, not evolution.    The authors do not deny that these backup systems evolved somehow: “For a single cell, the ability to quickly and efficiently respond to fluctuating environments is crucial and offers an obvious evolutionary advantage,” they postulate, suggesting that accidental duplication of genes was co-opted for this purpose.  They do not get into any details of how this might have happened, however, and their analysis seems more interested on the complexity and design benefit of the systems.    Their criteria for functional backups were stated thus: “Two lines of evidence could indicate a function’s direct benefit from existing redundancy: first is the evolutionary conservation of the functional overlap, and second is a nontrivial regulatory design that utilizes it.”  How many such systems exist in nature they could not say, because there have not been enough studies.  Many functionally equivalent copies of enzymes (isozymes) are known.  The genes that produce them are often regulated by different pathways.  Under stress, however, some can become coregulated to provide robustness against environmental irregularities or damaging mutations.The model that emerges is that although many isozymes are specialized for different environmental regimes, alarm signals induced by particular stress stimuli may call for their synergistic coexpression.  Here, RBCs provide functional specialization together with extreme flexibility in gene control that could be activated when sufficient stress has been applied.  For example, in yeast, glucose serves as a regulatory input for alternating between aerobic and anaerobic growth.  Its presence is detected by two separate and independent signaling pathways, one probing intracellular glucose concentrations and the other probing extracellular concentrations.They searched the literature and found several interesting ones that are described in detail in the paper.  “In all these cases, the common denominator is that one of the two duplicates is under repression in wild type and that that repression is relieved upon its partner’s mutation.”    This raises an interesting question – one that could have been asked by someone in the intelligent design movement.  They even answer a possible objection with a design principle:The extent to which genomic functional redundancies have influenced the way we think about biology can be appreciated simply by inspecting the vast number of times the word “redundancy” is specifically referred to in the biomedical literature (Fig. 5, which is published as supporting information on the PNAS web site).  Particularly interesting is the abundance with which it is addressed in studies of developmental biology (Fig. 5).  In fact, it is here that concepts such as “genetic buffering” and “canalization” first had been suggested.  Furthermore, the robustness of the developmental phenotypes such as body morphologies and patterning have been repeatedly demonstrated.  So the question is, are these redundancies simply leftovers of ancient duplications, or are they an additional component to the sophisticated machinery of cellular regulation?    In criticism, one may argue that many of the reported redundancies do not actually represent functionally equivalent genes but rather reflect only partial functional overlap.  In fact, knockout phenotypes have been described for a number of developmental genes that have redundant partners.  For these reasons, it has been suggested to define redundancy as a measure of correlated, rather than degenerate, gene functions.  Although these facts may suggest that redundancies have not evolved for the sake of buffering mutations, it has, in our opinion, little relevance to the question of whether they serve a functional role.  The interesting question is, then, can such a functional role for the duplicated state be inferred from the way the two genes are regulated?Along that line, they found that the amount of upregulation of one gene was often dependent on the regulation of the other.  This suggested to them that the sum of the expression of the two copies is nearly constant as a buffer against noise in the system.  When one line gets noisy, due to a mutation, the other responds with more signal.  They call this “dosage-dependent linear response.”  In some cases during development, the responsive overlap decreases as the organism grows.  In short, “The abundance of redundancies occurring in genes related to developmental processes, and their functional role as master regulators (Fig. 5) may be taken to suggest their utilization in either the flexibility or robustness of regulatory control.”    Some examples they give are even more complex.  RBCs may also be implicated in the resistance of some organisms to multiple drugs.  In some cases, each isoform can compensate equally for the other; in others, one of the forms is the main (the controller) and the other acts as the backup (the responder), only coming into play when the primary goes sour.  “One of the most profound and insightful of these recurring regulatory themes,” they exclaim, “is that, although both genes are capable of some functional compensation, disruption of the responder produces a significantly less deleterious phenotype than disruption of the controller”.  In evolutionary terms, why would the backup copy be better?A simple potential interpretation may suggest that although the controller is the key player performing some essential biological role, the responder is merely a less efficient substitute.  Yet, accepting the notion that redundancy could not have evolved for the sake of buffering mutations, this interpretation still is severely lacking.    A different, and more biologically reasonable, hypothesis accounting these asymmetries is that one of the functions of the responder is to buffer dosage fluctuations of the controller.  This buffering capacity requires a functional overlap that also manifests itself in compensations against the more rare event of gene loss.  Other models accounting for this assymetry are discussed further in this work, but our main point of argument is that this complex regulation of functionally redundant, yet evolutionarily conserved genes, strongly indicates utilization of redundancy.Their next subsection is called “Regulatory Designs.”  What emerges from their discussion of how each gene can regulate its partner is a complex picture: in one case, “redundancy is embedded within a more complex interaction network that includes a unidirectional responsive circuit in which the controller (dlx3) also represses its own transcription, whereas the responder (dlx7) is a positive autoregulator.”  More examples like this are described.  They predicted, and found, that RBCs could also regulate “downstream processes from variation and fluctuations arising from nongenetic noise.”  The net result is that by using these functional backup systems, the organism has more robustness against perturbations, yet more flexibility in a dynamic environment.    What is the fruit of this research?  Why should scientists look for these “regulatory designs” in the cell?  They offer an intriguing example.  It is known that one form of human muscular dystrophy occurs when a member of an RBC suffers a mutation.  Studies of this pair in mice, however, shows that the other member can respond by upregulating its expression.  It is thought a similar response might occur in humans.  “Inspired by the compensatory effect demonstrated by this RBC in mice, its artificial induction in humans by means of gene therapy has been suggested.  Although such modalities have not yet been realized, they suggest a fruitful possibility.”1Kafri, Levy and Pilpel, “The regulatory utilization of genetic redundancy through responsive backup circuits,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0604883103, published online before print July 21, 2006This is really a remarkable paper filled with inspiring possibilities.  If we can just think design instead of years of mindless mutations, we might find cures for debilitating diseases.  This paper has much of the obligatory evolutionspeak, but what does Darwinian thinking really contribute?  Nothing.  Although the researchers paid lip service to the evolutionary explanation that members of RBC pairs might have arisen through gene duplication, and that the coregulation might have provided a selectable fitness advantage, such language is really nothing more than the usual aftermarket sales pitch on the designed product.  The real heart of their argument was that design exists, it is functional, and we can learn from it in ways that could help mankind.  The future of design-theoretic science looks bright.(Visited 8 times, 1 visits today)FacebookTwitterPinterestSave分享0last_img read more

KimmyKu Baby Hair Clips Bows Accessories Barrettes – Very disappointed. A clip was missing and one was broke

first_imgProperly i can truthfully say we have hardly ever had hair accessories appear as nicely introduced as this tiny great deal which come packaged in an organza bag then a minimal treasure trove present box. I could convey to my youngest, the three 12 months outdated required to stash them in her room with her distinctive points as soon as they landed her eyes lit up. Both equally little ones beloved them to be truthful, every single clip is different and all of them are very in their individual way. My two very little girls seized upon one that seemed like a capturing star and also a shell form they felt specified the minimal mermaid would dress in. There are a blend of components and colors but all glance very well made. Some are crocodile clip and some are snap shut. They gasped aloud sorting as a result of this minimal ton and the arguments started out nearly immediatelymy youngest has fine hair with a curl to it and her hair is constantly in her eyes so a bobble or clip is required to maintaining the hair likely absent from her eyes in the quest to grow it a little bit for a longer period and not maintain trimming it in to a fringe. These are perfect for a side swept hair do and she is far more than delighted to have on them (whilst has not usually preferred hair accessories in the previous). Giving her a option from this box gives her extra independence and she is truly keen to pick her individual hair clip which is really sweet.I could not get more than on how adorable these are. The excellent is incredible and the assortment is brilliant. I can not hold out for my niece to dress in them.Ideal xmas present wonderful and well made with a lot of variety.Here are the specifications for the KimmyKu Baby Hair Clips Bows Accessories Barrettes:KimmyKu Soft Small Tiny Big Pretty Birthday Princess Baby Childs Kids infants newborn Toddlers little Girls Boutique Hair Bows Barrettes Snap Alligator Hair Clips Headpieces Accessories headbandsQTY:14 pcs assorted styles and colors hair bows clips exactlyt as picture show ,packed by pink decent knited gift box as picture showSize: assorted small middle and big size ,both Ok for thin and thick hair non slip ,great for kids age 0-6 year old.This decent and delicated hair clips set is the best christmas holiday festival gifts for niece granddaughter birthday ,costume party eventRemarks:for the pink knitted gift box ,the pink ribbon wrapped above on the case ,will be randomly send the pink ribbon edge with metallic finish ,or plain pink ribbon ,as picture show ,last_img read more

Current crop of archers can have another shot at Olympics

first_imgIndia’s archery campaign at the London Olympics ended on a disappointing note with Deepika Kumari going out in the first elimination round to home favourite Amy Oliver.Deepika had defeated the British girl quite easily whenever they had faced off previously, but at Lord’s on Wednesday, things turned out differently.This was a totally unexpected result. Deepika did not hit any 10s when required, which is very unusual. Normally, she compensates for her low scores by shooting a large number of 10s, but could not manage to do so here.She told us after her match that she did not feel any pressure during her match. However she struggled to assess the tricky conditions.As far as the other archers are concerned, Jayanta Talukdar did not put in a good performance though he was up against a top American.Rahul and Tarundeep made it to the second elimination round, before bowing out. But they showed fight which is a good sign.Chekrovolu Swuro seemed to just give it away after being in control. She first allowed her to draw level at 5-5 and then went down in the shoot-off.In the overall picture of the archers’ performance at the Olympics, the less than perfect start also had a role. They finished quite low down in the ranking round, which could have had an adverse impact on their morale.The fact that the conditions were quite tricky can be gauged from the fact that the topranked men’s archer, Brady Ellison of the United States, lost in the second round and later tweeted that he was thoroughly confused by the wind.advertisementAfter returning to India, one needs to find out what ingredient we are missing as we fail to crack the Olympic code despite going with high hopes. We need a long term programme for the Olympics.Age is no factor in archery and if the current batch can remain fit and focused, they can have another crack at the Olympics.(The writer is a two-time Olympian and Arjuna awardee)last_img read more

Puyol hands U-17 WC ticket to 1911 Bagan captains descendant

first_imgNew Delhi, May 15 (PTI) Spanish football legend Carles Puyol, on expected lines, attracted all the attention as the local organising committee of the FIFA U-17 World Cup today kick-started the ticket sales here. The former Barcelona central defender was engaged in a friendly match with Sports Minister Vijay Goel and his cabinet colleague Babul Supriyo, who is also the vice chairman of the LOC, along with the kids associated with the governments Mission XI Million programme. Tickets for the first FIFA tournament in the country will go live at exactly 19.11 hours tomorrow, paying a tribute to the year in which Indian football made history. It was the first time an Indian football team, Mohun Bagan FC, defeated an English side (East Yorkshire Regiment) and won the IFA Shield. Appropriately, Gauri Bhaduri, grand daughter-in-law of Shivdas Bhaduri, captain of that team, was handed over the first ticket by Puyol. Puyol expressed his wish to be a part of the tournament in October. “I was very curious and excited to discover the country and I am glad that I witnessed its rich culture,” Puyol said. “Indians will get the chance to see World Cup matches live and that experience is completely different from watching it on television. You can feel the energy in the stands. “At the FIFA U-17 World Cup, you can see the stars of the future. Indians should make the most of this opportunity and come in numbers to watch international teams play at home.” Goel said, “We have made sure that tickets are priced nominally, you can buy a world cup ticket for less than 50 rupees. So, there is no reason not to come and support this tournament in large numbers.” “I do not see this tournament as the conclusion, rather it is the start of the next revolution in Indian football and I need all your support to make the most of this amazing opportunity.” PTI AH PDS PDSadvertisementlast_img read more

Florida State Suspends Winston

first_imgTALLAHASSEE, Fla. — Florida State has suspended Jameis Winston for the entire game against Clemson on Sept. 20, extending its initial punishment of one half after the quarterback made “offensive and vulgar” comments about female anatomy earlier this week.Interim President Garnett S. Stokes and Ahletic Director Stan Wilcox announced the decision late Sept. 19. There had been criticism that the original punishment for Winston’s latest embarrassing off-field incident was too light.The statement released by the university read, “Based upon the results of our continuing investigation of Tuesday’s incident involving Jameis Winston, we have decided to not play him for the entire game against Clemson on Saturday night.”Several students tweeted Winston stood on campus and shouted a lascivious comment that may have derived from an internet meme.A university spokeswoman told The Associated Press Stokes was not available for comment; Wilcox could not be reached.The university also had initially announced that Winston would face internal discipline. Officials did not say why Winston was only benched for just a half and they did not provide details of the internal punishment.Coach Jimbo Fisher was asked about the half-game suspension after practice and said, “We’re in charge. It’s our team. That’s what we thought. We went with the consequences and we’re ready to move on.”Fisher also said after that practice that the President and Athletic Director are always involved in university policy, but declined to answer when asked if it’s normal for them to be involved in team discipline.“It was wrong and he made a mistake,” Fisher said. “He made a bad error in judgment. But that’s water under the bridge. We have to move on and get ready for this game. We’re 48 hours out and I’m going to focus on this football game.”The 20-year-old Winston addressed his inappropriate comments before a Sept. 17 practice: “I have to tone it down.” The Heisman Trophy winner has made similar comments after previous incidents.While playing for the Florida State baseball team, he was suspended for three games and completed 20 hours of community service after acknowledging he stole $32 worth of crab legs from a local grocery store in April.Before the football season, he said he had matured, learned what it takes to be a leader and understood that he needed to be more careful in his personal life.The school President and AD are admonishing him for doing just the opposite.“You know you have to overcome adversity, and that’s one thing at Florida State that we do,” Winston said. “We work on overcoming adversity. When I do get my opportunity to play, I’m going to do everything I can because I have to accept it.“That’s going to eat me up because I want to be out there on the field. I want to be out on the field with my team, but I did something so I have to accept the consequences.”Little known redshirt sophomore Sean Maguire will make his first college start for the top-ranked Seminoles in the Sept. 20 nationally televised game against No. 22 Clemson. He has only thrown 26 career passes and was the No. 3 quarterback before Jacob Coker was injured in 2013 then transferred to Alabama.“I wouldn’t say it’s a distraction, maybe at the time,” Maguire said about the incident. “Maybe for the first little bit, but once the news came out, practiced happened yesterday.“It makes me more confident knowing I get to go out there and play quarterback like we do in practice, like we do every day. I’m just looking forward to it, that’s all I can say.”Florida State is trying to repeat as national champions and the winner of the Clemson-Florida State matchup has played in the Atlantic Coast Conference title game the last five years.Sept. 20 will be the first game Florida State has played without Winston since the start of 2013 and they are 16-0 during that stretch.(KAREEM COPELAND)TweetPinShare0 Shareslast_img read more

Libraries computerised thanks to Hospitals Donation

first_img Electricity Cost of Service Study among the big agenda items at September 11 Cabinet meeting #MagneticMediaNews The Luxury of Grace Bay in Down Town Provo Facebook Twitter Google+LinkedInPinterestWhatsAppProvidenciales, TCI, February 9, 2017 – Libraries in the country which were without computers will see that changed thanks to a generous and modern donation by the TCI Hospitals this morning.Education Minister, Josephine Connolly with the Cecil Graham, Chief Librarian for the country were overjoyed at the gift of eight new computers which will add to the compliment already in Grand Turk and Provo and the HP desktops will give three other libraries what they do not have: computers.   “I’m happy that organizations like yours see it fit to step up to the plate, to help our children achieve their goals, and I can assure you also that they will look after these computers.”“With these available now the children are able to do their research because not all the time we are able to have the books, so they need to go on the internet.” – Cecil Graham, Chief LibrarianDaniel Carriere, CEO of TCI Hospitals says this is a gift from InterHealth Canada Corporate and that it is all about adding to the quality of life and ease for a good education.   “This is a small component of what InterHealth tries to do every year in terms of returning money and also our attention back to the community.”Detorrie Tennant, the Information Systems Manager at the Hospitals said the machines are not only new and state of the art, but they are earth friendly.   “Green, in that it has a very small power supply which burns not much electricity, and the screen which is the  most obvious thing is 21.5 inches, its very sharp.”Grand Turk and Provo libraries will each get one computer; two new computers will go to South Caicos, two to the library in Bottle Creek, North Caicos and two computers are earmarked for Kew, also in North Caicos.   The handover happened this morning at the Cheshire Hall Medical Centre. Recommended for youcenter_img Related Items:#magneticmedianews ALERT # 2 ON POTENTIAL TROPICAL CYCLONE NINE ISSUED BY THE BAHAMAS DEPARTMENT OF METEOROLOGY THURSDAY 12TH SEPTEMBER, 2019 AT 9 PM EDT Facebook Twitter Google+LinkedInPinterestWhatsApplast_img read more

Sony patent checks game load times to detect piracy

first_imgProtecting against piracy is something console manufacturers take very seriously due to the potential loss in revenue they believe comes with it. That’s part of the reason why consoles like the PS3 and Xbox 360 have regular system updates applied. If an issue or exploit is found, Sony/Microsoft can automatically patch it either over the Internet or off a disc before a new game is allowed to be played.For the PS4, Sony may be introducing a new test in order to determine whether you are attempting to play a pirate copy of a game. A validation check has been detailed in a new patent, entitled “Benchmark Measurement for Legitimate Duplication Validation,” that Sony filed for back in 2011 and which got published a few days ago that measures the load times of a game. If those times don’t fall within a specified range, the game is classed as suspicious and further validation checks are carried out to ensure piracy isn’t occurring.Such a validation system would require time ranges be specified on a per media and per game basis. So a game distributed on Blu-ray may have an average load time of 50 seconds, with the validation passing if the game loads in between 45 and 55 seconds. A different time would be required for the same game distributed over the PlayStation Network as it would typically load faster.The test performed doesn’t have to be time based, though. Sony could also monitor the data rate of the media transferring to the system. If it didn’t fall within a specified range then the game would be detected as loading from some other media, and therefore is more likely to be an illegal copy.It’s not known whether Sony intends to employ this system in the PS4, but it does offer a silent form of checking the games being loaded on the console are in fact legitimate. In fact, Sony wouldn’t need to use such a system until an exploit allowing copied games to run was found. So it could lay dormant as part of the firmware until it was required. Gamers wouldn’t even know it was there.My biggest issue/concern with such a system is how reliable it can be. Would a console that has a disc player that takes a little while to get spinning due to its age and wear start classing legitimate discs as illegal? A lot depends on how consistent the hardware being used is regardless of the where and when it was manufactured. Sony would also have to take into consideration the different iterations of the hardware it releases, and have some way of updating the load time averages for every single game release. It actually sounds like a big headache Sony would not want to manage.last_img read more