ST JOHN’S, Antigua (CMC):The front runners will jostle for the advantage heading into the Christmas break when the curtain rises on the fifth round of the Digicel Regional 4-Day Tournament this weekend.A potentially intriguing contest between hosts Leeward Islands Hurricanes and current leaders Jamaica Scorpions starts today at Warner Park in St Kitts.Also, two-time defending champions Guyana Jaguars face Trinidad & Tobago Red Force at the Guyana National Stadium, starting tomorrow, the same day that Windward Islands Volcanoes meet Barbados Pride at Windsor Park in Dominica.In Basseterre, momentum will be the key word for both the Hurricanes and Scorpions following contrasting results in the previous round of matches.The Hurricanes will be keen on regaining the energy they had from early in the season, after the weather in Port-of-Spain and defeat to the Volcanoes derailed them in the last two rounds of matches.In Guyana, The Jaguars will be looking to finish the first half of the season in pole position by exploiting a Red Force side low on confidence.This match could well be another absorbing contest, considering the results of matches between the two sides at this venue.Of the five matches, they have each won once, and it would be interesting to note that the Red Force has held the aces in the other three which have all been drawn.FIERCE RIVALRYIn Dominica, a compelling contest is expected between the Volcanoes and Pride in what is typically one of the fiercest rivalries in the R4Day.The Volcanoes will be pumped up to face a team against whom they typically rise to the challenge to confront, following their stunning, come-from-behind victory over the Hurricanes in the previous round.At the same time, the Pride – boosted by a number of returning West Indies players – were engaged in an engrossing battle with the Jaguars in between the showers, but had to settle for a draw.Scorpions top of the table on 46.8 points, while defending champions Guyana Jaguars sit in second position on 44 points with Barbados Pride on 43.2 points.Leewards Hurricanes are on 36.6 points, Windwards Volcanoes 35.2 and Red Force 32.4.The fifth round of the Digicel Regional 4-Day Tournament will be followed by a long break for the Christmas/New Year’s holidays before the Regional Super50 Tournament sets in.
Arroyo and Leviste were part of the team that won the same silver medal in the 2011 Games but wasn’t able to repeat the feat in the 2013 and 2015 outings.Malaysia won the gold while Thailand settled for bronze.FEATURED STORIESSPORTSEnd of his agony? SC rules in favor of Espinosa, orders promoter heirs to pay boxing legendSPORTSRedemption is sweet for Ginebra, Scottie ThompsonSPORTSMayweather beats Pacquiao, Canelo for ‘Fighter of the Decade’ FILE PHOTO – Toni Leviste, aboard Loribri, competes in the Longines Global Champions Tour event in Florida. Above left, Toni receives a prize for her lofty finish.The Philippines took a spot in the podium of the 2017 Southeast Asian Games after taking the silver medal in the show jumping team event in equestrian Saturday in Kuala Lumpur, Malaysia.Antoinette Leviste and Joker Arroyo teamed up with Chiara Sophia Amor and Colin John Syquia for the second-best finish in the event.ADVERTISEMENT Search on for 5 Indonesians snatched anew in Lahad Datu LATEST STORIES OSG plea to revoke ABS-CBN franchise ‘a duplicitous move’ – Lacson MOST READ Trending Articles PLAY LIST 00:50Trending Articles02:11SEA GAMES 2019: PH’s Nesthy Petecio boxing featherweight final (HIGHLIGHTS)08:07Athletes treated to a spectacle as SEA Games 2019 officially ends06:27SEA Games 2019: No surprises as Gilas Pilipinas cruises to basketball gold05:02SEA Games 2019: Philippines clinches historic gold in women’s basketball05:21Drama in karate: Tsukii ‘very sad’ over coach’s bullying, cold shoulder03:24PH’s James Palicte boxing light welterweight final (HIGHLIGHTS) Britain’s Prince Harry and Meghan Markle to give up royal titles What’s in store for your animal sign this year Sports Related Videospowered by AdSparcRead Next Marcosian mode: Duterte threatens to arrest water execs ‘one night’ National Historical team rescues Amorsolos, artifacts from Taal Don’t miss out on the latest news and information. View comments Bishop Baylon encourages faithful in Albay to help Taal evacuees Police seize P68-M worth of ‘shabu’ in Pasay Clarice Patrimonio wins silver in tennis Hotdog’s Dennis Garcia dies
Famed EVOLVE MMA to hold global tryouts Lights inside SMX hall flicker as Duterte rants vs Ayala, Pangilinan anew Ginebra beats Meralco again to capture PBA Governors’ Cup title Sports Related Videospowered by AdSparcRead Next “If we’re not able to complete the documents of Greg, our situation will get harder because we have to choose between those three guys who we will designate as our naturalized player,” added Guiao, who is hoping that Slaughter, Filipino-German Christian Standhardinger and Fil-American Stanley Pringle will be given the green light by Fiba to play as locals.Guiao said one the requirements Slaughter needs to present to Fiba is a proof that he was able to secure a Philippine passport before he turned 16 years old.But that’s not the only thing that Slaughter is worried about.“After that, next is, I gotta worry about that giant Haddadi out there,” said Slaughter, referring to Iran’s 7-foot-2 big man Hamed Haddadi.“But you know, with coach Yeng and all my teammates around, I’m confident. I feel like we can take on any team, we got a great group of guys, all great attitudes, all really excited and it gets me excited to play.”ADVERTISEMENT Tim Cone, Ginebra set their sights on elusive All-Filipino crown Gretchen Barretto’s daughter Dominique graduates magna cum laude from California college Japeth Aguilar embraces role, gets rewarded with Finals MVP plum Lights inside SMX hall flicker as Duterte rants vs Ayala, Pangilinan anew Nadine Lustre’s phone stolen in Brazil Despite representing the country before as a member of the original Smart Gilas program created in 2009, Slaughter said he still needs to meet some requirements by Fiba to be allowed to play as a local.“First of all, my main problem is getting the remaining documents they’re asking for with the short window. So I gotta worry about that,” Slaughter told INQUIRER.net.FEATURED STORIESSPORTSGinebra beats Meralco again to capture PBA Governors’ Cup titleSPORTSJapeth Aguilar wins 1st PBA Finals MVP award for GinebraSPORTSTim Cone still willing to coach Gilas but admits decision won’t be ‘simple yes or no’National team coach Yeng Guiao said Slaughter’s predicament further complicates the team’s situation as far as coming up with the final lineup for the fourth window of the Fiba World Cup Asian qualifiers against Iran and Qatar beginning on September 13 in Tehran.“We have to be certain on the situation of Greg, Christian (Standhardinger) and Stanley (Pringle),” Guiao said after Monday night’s practice as he held out on announcing his 12-man lineup until something concrete unfolds. View comments Carpio hits red carpet treatment for China Coast Guard PLAY LIST 02:14Carpio hits red carpet treatment for China Coast Guard02:56NCRPO pledges to donate P3.5 million to victims of Taal eruption00:56Heavy rain brings some relief in Australia02:37Calm moments allow Taal folks some respite03:23Negosyo sa Tagaytay City, bagsak sa pag-aalboroto ng Bulkang Taal01:13Christian Standhardinger wins PBA Best Player award Gov’t to employ 6,000 displaced by Taal Allen Durham still determined to help Meralco win 1st PBA title LATEST STORIES Greg Slaughter of Barangay Ginebra shares a laugh with Marcio Lassiter of San Miguel Beer during the national team pool practice Monday night. Slaughter and Lassiter were both part of the original Smart Gilas program established in 2009. Photo by Tristan Tamayo/INQUIRER.netIt took almost a decade for Greg Slaughter to be back serving the national team.But before the Barangay Ginebra center can actually play for the Philippines in the international stage, he must first iron out the kinks of his eligibility.ADVERTISEMENT Don’t miss out on the latest news and information. MOST READ
Gretchen Barretto’s daughter Dominique graduates magna cum laude from California college Will you be the first P16 Billion Powerball jackpot winner from the Philippines? Orizu played his first game back since suffering a high ankle sprain at the start of the second round in late October and he promised to give his all to help the Tamaraws break into the Final Four.“I have to push myself because it’s really important for the team and me,” said Orizu after FEU’s 79-74 win over National University in the UAAP Season 81 men’s basketball tournament Sunday at Smart Araneta Coliseum.FEATURED STORIESSPORTSGinebra beats Meralco again to capture PBA Governors’ Cup titleSPORTSJapeth Aguilar wins 1st PBA Finals MVP award for GinebraSPORTSGolden State Warriors sign Lee to multiyear contract, bring back ChrissOrizu was the missing piece in FEU’s rotation during its four-game skid that brought the Tamaraws to as low as sixth in the standings during the middle part of the second round.FEU has since recovered and owns a 7-6 card to tie University of the Philippines for the fourth seed. Lights inside SMX hall flicker as Duterte rants vs Ayala, Pangilinan anew Lights inside SMX hall flicker as Duterte rants vs Ayala, Pangilinan anew Ateneo secures twice-to-beat, downs La Salle anew Although Orizu was medically cleared in FEU’s last game in a 80-61 rout of University of the East but it was just in the Tamaraws’ match against the Bulldogs that he was slotted in.Orizu played for nine minutes and had six points with five rebounds.And it’s not just FEU’s chance at the Final Four that Orizu’s thinking about. He has never missed the Final Four and he has no plans of missing his first semifinals.“I’ve never not been in the Final Four since I’ve played in the UAAP, and I don’t want to give that up now because of the ups and downs of my team and my injury too,” said Orizu. “I just take it as a motivation and push myself towards the game.”“We just have to play together as a team, we have to trust each other, trust the coaches, and trust the system. Play like brothers and we got this.”ADVERTISEMENT Allen Durham still determined to help Meralco win 1st PBA title Tim Cone, Ginebra set their sights on elusive All-Filipino crown Gov’t to employ 6,000 displaced by Taal Far Eastern University center Prince Orizu was ready to push his body to its utmost limit despite just a few days removed from his injury recovery.ADVERTISEMENT Carpio hits red carpet treatment for China Coast Guard PLAY LIST 02:14Carpio hits red carpet treatment for China Coast Guard02:56NCRPO pledges to donate P3.5 million to victims of Taal eruption00:56Heavy rain brings some relief in Australia02:37Calm moments allow Taal folks some respite03:23Negosyo sa Tagaytay City, bagsak sa pag-aalboroto ng Bulkang Taal01:13Christian Standhardinger wins PBA Best Player award Nadine Lustre’s phone stolen in Brazil MOST READ Sports Related Videospowered by AdSparcRead Next Japeth Aguilar embraces role, gets rewarded with Finals MVP plum For the complete collegiate sports coverage including scores, schedules and stories, visit Inquirer Varsity. LATEST STORIES Don’t miss out on the latest news and information. View comments
A ruling of the Commercial Court at the Temple of Justice which should have established whether or not it has the legal rights to proceed with hearings into a US$10.7M lawsuit filed against the Government of Liberia (GOL) by a Lebanese businessman, George Haddad, is yet to be handed down by the court.Haddad, the Chief Executive Officer (CEO) of Prestige Motor Corporation and Alliance Motor Corporation, is pursing the debt action against the government..Surprisingly, government lawyers are seeking to have the court remove itself from the case. They also want to have a portion of the debt action against GOL excluded from the trial and are seeking to have the whole case thrown out.In early February, the Resident Chief Judge of the three-judge panel that is presiding over the court postponed ruling on the various issues. Judge Eva Mappy Morgan also said the panel of judges was considering conducting an in-chambers review of records from both parties.She publicly made the assertion immediately after they listened to arguments from both parties in response to the government’s request.Interestingly, up to present, Judge Morgan and panel have not informed the lawyers when they will bring down their decision.The reason for the delay is unknown, but the Daily Observer has learned that authorities at the Ministry of Finance were considering negotiating with Haddad to reduce the money.The legal expert did not say if Mr. Haddad has agreed to have the matter settled out of court. Hailing the court’s initial decision to hear arguments in the matter, the legal expert said, “We are pleased that the judges are thoroughly examining these serious legal issues and believe that the court has chosen the absolutely correct path to address where the case is now, but we have not been told when that would happen,” the source told this paper.Apparently, the source said, government was doing that to discourage other entities from taking GOL to the Commercial Court regarding contracts and debts incurred by past governments.“The challenging part is that if the court denies the request, other organizations would (be encouraged) to go to the Commercial Court for redress on contracts or services they performed for past administrations, especially during the interim periods, and have not been paid,” the legal source added.The case alleges that government, from 2000 to 2008, hired the services of Mr. Haddad, who sold and repaired vehicles and also supplied spare parts amounting to US$10.7M to several state owned institutions (SOI). However those SOIs are yet to pay their debts, despite Mr. Haddad’s persistent claims.Among the vehicles for which GOL owes Haddad are Cherokee and Land Rover Leon.Though GOL has admitted owing Mr. Haddad, its lawyers insist that the Commercial Court is not the proper court under the law to hear and decide the case.Justifying their argument, Cllr Augustine Fayia said, “The Commercial Court was established in 2010, which means the law that created it prevents the court from hearing cases prior to its establishment.”He further argued that if the court continues with the matter, it would be a complete violation of the Constitution and the Act that created it.He pleaded that the court advise Haddad’s lawyers to file their complaint to the appropriate court, but did not mention which court was the appropriate one to take the case.Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window)
Arsenal midfielder Mesut Ozil has been named in L’Equipe’s worst XI of World Cup 2018.The German international flopped in Russia as he and his compatriots failed to make it out of a weak group. Mesut Ozil looks dejected after Germany’s defeat to South Korea. silverware possible xi Tottenham v Brighton LIVE: talkSPORT commentary and team news for Boxing Day opener How Liverpool could line up at Leicester with midfielder set for lengthy absence England’s most successful clubs of the past decade, according to trophies won predicted Latest Premier League news Every current Premier League club’s best kit from the past decade How Man United could line up for Newcastle clash – will Pogba start? smart causal How Chelsea could line up against Southampton – what system will Lampard play? NEW ERA The 2014 World Champions ended up losing to Mexico and South Korea, despite a win over eventual quarter-finalists Sweden.Sami Khedira and Thomas Muller, who were also guilty of poor performances, joined Ozil, who received an average of three out of 10 from the French newspaper, in the team.Fellow Premier League stars Willy Caballero (Chelsea and Argentina) and Kelechi Iheanacho (Leicester City and Nigeria) also made the XI, which you can see below. gameday possible standings Tottenham predicted XI to face Brighton with Mourinho expected to make big changes How Arsenal could line up in Arteta’s first official game in charge – Ozil return? ALTERED How the Premier League table could change after the Boxing Day fixtures 1 who plays? REVEALED Which teams do the best on Boxing Day in the Premier League era?
The developer of Letterkenny’s biggest retail park is being urged to locate public toilets in the outlet.At present there are no public toilet facilities at the Link Retail Park which includes a number of major shops including Argos, TX Maxx, Marks and Spencer, Dunnes Stores, Halfords and Smyths Toys.However local town councillor Jimmy Kavanagh said there is a real need for public toilets in the area. He has asked the local town council to approach the developer of the park to see what can be done.“The retail park has become a hugely busy part of our town. It does not have any public toilet facilities and we can continue to rely on the goodwill of cafes and restaurants in the area,” he said.A spokesman for the council told Cllr Kavanagh that the issue has been discussed with the developer who is giving it some consideration.LEAVE YOUR COMMENT BELOW © 2011 donegaldaily.com, all Rights ReservedThe copying, republication or redistribution of donegaldaily.com Content, including by framing or similar means, is expressly prohibited by law.Follow us on www.twitter.com/donegaldailyFollow us on www.facebook.com/donegaldailySell anything on www.donegaldailyclassifieds.com DEVELOPER MAY PROVIDE SOME ‘RELIEF’ FOR BUSY LETTERKENNY SHOPPERS! was last modified: January 21st, 2012 by StephenShare this:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Reddit (Opens in new window)Click to share on Pocket (Opens in new window)Click to share on Telegram (Opens in new window)Click to share on WhatsApp (Opens in new window)Click to share on Skype (Opens in new window)Click to print (Opens in new window)Tags:LINK RETAIL PARKTOILET
Finn Harps manager Ollie Horgan has flagged his concern over the scoring threat that Galway United pose ahead of this Saturday evening’s League of Ireland Premier Division game at Eamonn Deacy Park (kick-off 7.00). Despite the defeat to Cork City on Tuesday night at Turner’s Cross the Tribesmen scored three goals against a side renowned for their defensive strengths as well as still being challengers for the league title.Since that game, however, Galway have parted company with their manager Tommy Dunne so it will be interesting to see what impact that has on the home team’s performance against Harps. Often it has a positive effect so the visitors will have to be very vigilant at the back as they try to get a at least a point after the recent eight-match losing run.“Galway have a very good, footballing side. They also have one of the best players in the league in Ryan Connolly. Galway scored three goals in Cork last week and two in Tallaght which very few teams do” said Horgan whose side hasn’t found the net in the last eight matches.Damian McNulty (knee) is not ready return this weekend according to the manager while he will also be missing Adam Hanlon who shipped a very heavy knock in the recent game against Cork City at Finn Park. Barry Molloy and Gareth Harkin are doubtful while Josh Mailey is unavailable due to college commitments in the UK.The record from the previous league games this season is a win each. Galway took the three points in April with a second half Vinny Faherty goal. In Ballybofey at the beginning of July it was a second half Sean Houston goal that gave Harps a 1-0 victory. That was the club’s last points in the Premier Division so it would be a huge relief if the visitors could get either a draw or a win at Eamonn Deacy Park tomorrow evening. Team NewsInjured: Damien McNulty, Adam HanlonDoubtful: Barry Molloy, Gareth HarkinUnavailable: Josh MaileySuspended: NoneRECORD AGAINST GALWAY (All Competitions)Friday’s game will be the 68th meeting of the two clubs, and the 35th to be played in Galway. This includes meetings with Galway United, Galway FC and Galway Rovers.Total Games: 67 (34 in Galway)Harps Wins: 21 (8 in Galway)Galway Wins: 26 (15 in Galway)Draws: 20 (13 in Galway)Harps Goals: 99 (53 in GalwayGalway Goals: 115 (69 in Galway) LAST 10 GAMES v GALWAY13-Jun-09 Finn Harps 0-3 Galway United (FAI Cup)29-Mar-14 Finn Harps 1-1 Galway FC (First Division)05-May-14 Galway FC 1-0 Finn Harps (League Cup)16-May-14 Galway FC 1-1 Finn Harps (First Division)18-Jul-14 Finn Harps 0-0 Galway FC (First Division)20-Sep-14 Galway FC 3-0 Finn Harps (First Division)09-Mar-15 Galway United 3-2 Finn Harps (League Cup)08-Apr-16 Galway United 1-0 Finn Harps (Premier Division)18-Apr-16 Galway United 0-0 Finn Harps (4-2 on penalties) (League Cup)8-Jul-16 Finn Harps 1-0 Galway United (Premier Division)Galway have scoring potential – Harps boss Horgan was last modified: September 30th, 2016 by StephenShare this:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Reddit (Opens in new window)Click to share on Pocket (Opens in new window)Click to share on Telegram (Opens in new window)Click to share on WhatsApp (Opens in new window)Click to share on Skype (Opens in new window)Click to print (Opens in new window)
It’s sometimes difficult to assess the impact of a scientific paper when it is first published, but one that came out on the cover of Nature today has potential to equal the discovery of the genetic code. The leading science journal reported the discovery of a second genetic code – the “code within the code” – that has just been cracked by molecular biologists and computer scientists. Moreover, they used information technology – not evolutionary theory – to figure it out. The new code is called the Splicing Code. It lives embedded within the DNA. It directs the primary genetic code, in very complex but now predictable ways, how and when to assemble genes and regulatory elements. Cracking this code-within-a-code is helping elucidate several long-standing mysteries about genetics that emerged from the Human Genome Project: Why are there only 20,000 genes for an organism as complex as a human being? (Scientists had expected far more.) Why are genes broken up into segments (called exons), separated by non-coding elements (called introns), and then spliced together after transcription? And why are genes turned on in some cells and tissues, but not in others? For two decades molecular biologists have been trying to figure out the mechanisms of genetic regulation. This important paper represents a milestone in understanding what goes on. It doesn’t answer all the questions, but it shows that an inner code exists – a communication system that can be deciphered so clearly, that the scientists could predict what the genome would do in certain situations with uncanny accuracy. Imagine hearing an orchestra in an adjacent room. You open the door and look inside, and find just three or four musicians producing all that sound. That’s what co-discoverer Brendan Frey said said the human genome is like. We could only find 20,000 genes, but we knew that a vast array of protein products and regulatory elements were being produced. How? One method is alternative splicing. Different exons (gene elements) can be assembled together in different ways. “For example, three neurexin genes can generate over 3,000 genetic messages that help control the wiring of the brain,” Frey said. The paper explains right off the bat that 95% of our genes are known to have alternative splicing, and in most cases, the transcripts are expressed differently in different cell and tissue types. Something must control how those thousands of combinations are assembled and expressed. That’s the job of the Splicing Code. Readers wanting a quick overview can read the Science Daily article, “Researchers Crack ‘Splicing Code,’ Solve a Mystery Underlying Biological Complexity.” It says, “Researchers at the University of Toronto have discovered a fundamentally new view of how living cells use a limited number of genes to generate enormously complex organs such as the brain.” In Nature itself, Heidi Ledford led off with an article called “The code within the code.”1 Tejedor and Valc�rcel followed with “Gene regulation: Breaking the second genetic code.2 Then the main dish was the paper by the University of Toronto Team led by Benjamin J. Blencowe and Brendan J. Frey, “Deciphering the splicing code.”3 The paper is a triumph of information science that sounds reminiscent of the days of the World War II codebreakers. Their methods included algebra, geometry, probability theory, vector calculus, information theory, code optimization, and other advanced methods. One thing they had no need of was evolutionary theory, which was never mentioned in the paper.4 Their abstract reverberates with the dramatic tension of a rousing overture:Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.The interdisciplinary team that cracked the code consists of specialists from the Department of Electrical and Computer Engineering as well as the Department of Molecular Genetics – and Frey works for Microsoft Research. Like the codebreakers of old, Frey and Barash developed “a new computer-assisted biological analysis method that finds ‘codewords’ hidden within the genome.” Taking vast amounts of data generated by the molecular geneticists, the group “reverse-engineered” the splicing code until they could predict how it would act. Once they got a handle on it, they tested it with mutations, and watched exons get inserted or deleted as they predicted. They found that the code can even cause tissue-specific changes, or act differently when the mouse is an embryo or an adult. One gene, Xpo4, is implicated in cancer; they noted that “These findings support the conclusion that Xpo4 expression must be tightly controlled such that it is active during embryogenesis but downregulated in adult tissues, to avoid possible deleterious consequences including oncogenesis” (cancer). It appears they were quite astonished at the level of control they were witnessing. Intentionally or not, Frey used the language of intelligent design – not that of random variation and selection – as the key to their approach: “Understanding a complex biological system is like understanding a complex electronic circuit.” Heidi Ledford said that the apparent simplicity of the Watson-Crick genetic code, with its four bases, triplet codons, 20 amino acids and 64 DNA “words” – conceals a universe of complexity beneath the surface.1 The Splicing Code-within-the-code is much more complex:But between DNA and proteins comes RNA, and an expanding realm of complexity. RNA is a shape-shifter, sometimes carrying genetic messages and sometimes regulating them, adopting a multitude of structures that can affect its function. In a paper published in this issue (see page 53), a team of researchers led by Benjamin Blencowe and Brendan Frey of the University of Toronto in Ontario, Canada, reports the first attempt to define a second genetic code: one that predicts how segments of messenger RNA transcribed from a given gene can be mixed and matched to yield multiple products in different tissues, a process called alternative splicing. This time there is no simple table – in its place are algorithms that combine more than 200 different features of DNA with predictions of RNA structure.The work highlights the rapid progress that computational methods have made in modelling the RNA landscape. In addition to understanding alternative splicing, informatics is helping researchers to predict RNA structures, and to identify the targets of small regulatory snippets of RNA that do not encode protein. “It’s an exciting time,” says Christopher Burge, a computational biologist at the Massachusetts Institute of Technology in Cambridge. “There’s going to be a lot of progress in the next few years.”Informatics – computational biology – algorithms and codes – such concepts were never a part of Darwin’s vocabulary as he developed his theory. Mendel had a vastly oversimplified computational model of how traits could be sorted out during inheritance, but even then, the idea that traits were encoded awaited discovery till 1953. Now we see that the original genetic code is itself subject to an even more complex embedded code. These are revolutionary ideas. And there are indications of even further levels of control. For instance, RNA and proteins have a three-dimensional structure, Ledford reminds us. The functions of the molecules can change when the shape changes. Something must control the folding so that the 3-D structure performs as required for function. And then the access to genes appears to be regulated by another code, the histone code, that is encoded by molecular markers or “tails” on the histone proteins that serve as nuclei for DNA coiling and supercoiling. Ledford spoke of an “ongoing renaissance in RNA informatics” characterizing our time. Tejedor and Valc�rcel agreed with the complexity concealed by the simplicity.2 “At face value, it all sounds simple: DNA makes RNA, which then makes protein,” they began. “But the reality is much more complex.” We learned in the 1950s that the basic genetic code is shared by all living organisms from bacteria to humans. But it soon became apparent that there was a bizarre, counter-intuitive feature in complex organisms (eukaryotes): their genomes were interrupted by introns that had to be snipped out so that the exons could be spliced together. Why? Now the fog is lifting: “An advantage of this mechanism is that it allows different cells to choose alternative means of pre-mRNA splicing and thus generates diverse messages from a single gene,” they explained. “The variant mRNAs can then encode different proteins with distinct functions.” You get more information out of less code – provided you have a code-within-the-code that knows how to do it. What makes cracking the splicing code so difficult is that the factors controlling what exons get assembled is determined by multiple factors: sequences adjacent to the exon boundaries, sequences in the exons, sequences in the introns, and regulatory factors that either assist or inhibit the splicing machinery. Not only that, “the effects of a particular sequence or factor can vary depending on its location relative to the intron�exon boundaries or other regulatory motifs,” Tejedor and Valc�rcel explained. “ The challenge, therefore, is to compute the algebra of a myriad of sequence motifs, and the mutual relationships between the regulatory factors that recognize them, to predict tissue-specific splicing.” To solve the puzzle, the team fed the computer huge amounts of data on RNA sequences and the conditions under which they formed. “The computer was then asked to identify the combination of features that could best explain the experimentally determined tissue-specific selection of exons.” In other words, they reverse-engineered the code. Like WWII codebreakers, once they knew the algorithm, they could make predictions: “It correctly identified alternative exons, and predicted their differential regulation between pairs of tissue types with considerable accuracy.” And like a good scientific theory, the discovery led to new insights: “This allows reinterpretation of the function of previously defined regulatory motifs and suggests previously unknown properties of known regulators as well as unexpected functional links between them,” they said. “For instance, the code inferred that the inclusion of exons that lead to truncated proteins is a common mechanism of gene-expression control during the transition between embryonic and adult tissues.” Tejedor and Valc�rcel see the publication of the paper as an important first step: “revealing the first piece of a much larger Rosetta Stone required to interpret the alternative messages of our genomes.” Future work will undoubtedly improve our knowledge of this new code, they said. In their ending, they referred to evolution briefly in a curious way: not to say that evolution produced these codes, but that progress will require understanding how codes interact. Another surprising possibility is that the degree of conservation seen so far raises the possibility of “species-specific codes” –The code is likely to work in a cell-autonomous manner and, consequently, may need to account for more than 200 cell types in mammals. It will also have to deal with the extensive diversity of alternative-splicing patterns beyond simple decisions of single exon inclusion or skipping. The limited evolutionary conservation of alternative-splicing regulation (estimated to be around 20% between humans and mice) opens up the question of species-specific codes. Moreover, coupling between RNA processing and gene transcription influences alternative splicing, and recent data implicate the packing of DNA with histone proteins and histone covalent modifications – the epigenetic code – in the regulation of splicing. The interplay between the histone and the splicing codes will therefore need to be accurately formulated in future approaches. The same applies to the still poorly understood influence of complex RNA structures on alternative splicing.Codes, codes, and more codes. The near silence about Darwinism in any of these papers suggests that old-school evolutionary theorists will have a lot to ponder after reading these papers. Meanwhile, those excited about the biology of codes will be on the cutting edge. They can play with a cool web tool the codebreakers created to stimulate further research. It can be found at the University of Toronto site, called WASP – “Website for Alternative Splicing Prediction.” Visitors will look in vain for anything about evolution here, despite the old maxim that nothing in biology makes sense without it. A new version for the 2010s might read, “Nothing in biology makes sense except in the light of informatics.”1. Heidi Ledford, “The code within the code,” Nature 465, 16-17 (06 May 2010) | doi:10.1038/465016a.2. J. Ram�n Tejedor and Juan Valc�rcel, “Gene regulation: Breaking the second genetic code,” Nature 465, 44-46 (06 May 2010) | doi:10.1038/465045a.3. Yoseph Barash, John A. Calarco, Weijun Gao, Qun Pan, Xinchen Wang, Ofer Shai, Benjamin J. Blencowe and Brendan J. Frey, “Deciphering the splicing code,” Nature 465, 53-59 (06 May 2010) | doi:10.1038/nature09000.4. “Conservation” information is mentioned several times, but refers only to a measure of sequence similarity between species, e.g., between mice and human genomes. Conservation does not have evolutionary significance without begging the question of evolution.We are happy to bring you this story on the day of its release. It may be one of the really big science papers of the year, or decade. It could be Nobel Prize material. (Any great discovery is, of course, surrounded by the work of many other teams, as was the work of Watson and Crick.) What more can we add as commentary other than, “Wow”? This is amazing confirmation of design, and a huge challenge to the Darwin Empire. It will be interesting to see how they try to recast their simplistic 19th-century story of random mutation and natural selection in light of this. Did you catch what Tejedor and Valc�rcel said? Species may have their own “species-specific” codes. “The interplay between the histone [epigenetic] and splicing codes will therefore need to be accurately formulated in future approaches,” they said. Being translated, that means: “Darwinists need not apply. You don’t have the skills to handle this.” If the plain-old Watson-Crick genetic code was a challenge to Darwinism, how now with the Splicing Code generating thousands of transcripts out of the same genes? On top of that, the Epigenetic Code controls the context of gene expression. It may well be that the arrangement of chromosomes inside the nucleus plays a kind of coding role in the regulation of gene expression, too. Who knows what other codes are involved in this incredible “interplay” we have only begun to read, like a Rosetta Stone just beginning to poke above the sand? Now that we are thinking codes and informatics, all kinds of new research paradigms come to mind. What if the genome acts partly like a storage area network? What if there is cryptography going on, or compression algorithms? We should be thinking advanced information systems and storage technologies. Maybe we will find some steganography even. Undoubtedly there are additional robustness mechanisms, like backups and retrieval – perhaps that helps explain pseudogenes. Whole-genome duplications may be responses to stress; other anomalies may be due to antivirus activity. Some of these trails may prove useful markers for historical events that have nothing to do with universal common ancestry, but open up comparative genomics in terms of informatics and design for robustness, and the understanding of disease. The end of it all is an organism functioning in the world. Think of a tiger: strong, sleek, unified, with a coat of fur marked with stripes, eyes and ears pointed forward, stalking through the jungle, equipped with all the muscles and bones and senses and behaviors it needs to live through the days and nights of a planet orbiting a star. Above it are birds flying through the canopy. Below are snails and small reptiles and ants. Fish are darting in the river. Hundreds of species of plants each know how to send their roots down and their leaves up and when to produce their flowers and fruits. A team of human scientists carries their video cameras into the jungle hoping to remotely trigger them and capture footage of the elusive tiger. In the soil below and within and without all these other organisms, trillions of microbes are functioning in their microcosmos. All this is happening because of molecular codes translating and regulating chemistry into directed function. What philosophers in ancient times could possibly have known that this level of computational, information-based complexity undergirded the stuff of life? We are the generation blessed to discover these realities. Darwinists are in for rough going ahead. The discoverers tried mutating the Splicing Code and got cancers and mistakes. How are you going to navigate a fitness landscape now, when it is a minefield of catastrophes waiting to happen when one starts mucking with all these intertwined codes? We know there is some built-in robustness and tolerance, but the picture emerging is a highly-complex, engineered, optimized informatics system – not a random arrangement of parts that can be endlessly tinkered with. The whole idea of code is an intelligent design concept. A. E. Wilder-Smith used to emphasize this. A code implies a convention between two parties. Convention – coming together – is an agreement in advance. It implies planning and purpose. The symbol SOS, he would say, we use by convention as a sign of distress. SOS does not look like distress. It does not smell like distress. It does not feel like distress. Nobody would know it means distress unless they understand the convention. In the same way, the codon for alanine, GCC, does not look, smell or feel like alanine. It would have nothing to do with alanine unless there were a pre-planned convention between two coding systems – the protein code and the DNA code – that “GCC shall mean alanine.” To convey that convention, a family of translators, the aminoacyl-tRNA-synthetases, are employed to translate one code into the other. That should have nailed the case for design in the 1950s, and many creationists preached it effectively. But the evolutionists are like fast-talking salesmen. They wove their just-so stories about Tinker Bell zapping the code and creating new species by mutation and selection and convinced many that miracles can still happen. OK, well now it’s 2010 and we have the Epigenetic Code and the Splicing Code, two codes much more complex and dynamic than the simple DNA code. We have codes within codes, codes above and below codes – a hierarchy of codes. They can’t just stick their finger in the pistol this time and bluff their way out of it with smooth talking now, not with cannons to the left of them and cannons to the right of them, a whole arsenal aimed at their vital parts. This is a game changer. The informatics age has grown around them and they are has-beens, like pike-thrusting Greeks facing modern tanks and helicopters. Sad to say, they don’t realize it; or if they do, they have no intention of conceding. In fact, some of the worst and most vicious, intolerant and hateful anti-creationist, anti-design rhetoric in recent memory has been pouring forth from the Darwin-controlled journals and newspapers this week, right when the Splicing Code paper was being published. Some examples will be forthcoming. And as long as they have the microphones and control the institutions, many people are going to be misled into thinking they still have the high ground in science. We bring you this material for you to read, study, understand, and arm yourselves with the information you need to combat bigoted bluffing blather with truth. Now go do it.(Visited 69 times, 1 visits today)FacebookTwitterPinterestSave分享0
27 March 2008Bafana Bafana scored a stylish and convincing 3-0 victory over world number 26 Paraguay at the Super Stadium in Atteridgeville on Wednesday evening with what was undoubtedly their best performance yet under coach Carlos Alberto Parreira.The victory was the first for South Africa over South American opposition in 10 outings, making the emphatic nature of the win all the more astonishing.Adding further gloss to the result is the fact that the Paraguayans entered the contest as the team on top of the standings in South American 2010 World Cup qualifying, ahead of world number one and two, Argentina and Brazil.Bafana Bafana’s effort satisfied coach Parreira and the fans. The supporters were in hearty voice throughout, with vuvuzelas blearing, as they witnessed a fluid, efficient and entertaining team in action.‘Everything went right’“I think the philosophy is there. The shape is there,” said Parreira afterwards, as he reflected on a superb performance in which he admitted “everything went right”.He also hit back at critics who had suggested that Bafana Bafana employed a system that was too defensive. Parreira said it wasn’t about the number of strikers, rather it was about getting players into the right areas and South Africa certainly managed to do that.As Parreira suggested, it was a complete performance and that meant that it at long last contained good finishing.One of the goals – the second – was scored by Benni McCarthy, his 30th for Bafana Bafana, which took him out of a tie with Shaun Bartlett for the most goals scored for South Africa. Captain Aaron Mokoena, meanwhile, equaled Bartlett’s record of 74 appearances for the team.Attacking intentFrom the opening whistle, the home team showed attacking intent and they were almost rewarded early on when Teko Modise let fly with a powerful shot that beat Paraguay’s goalkeeper Justo Villar but was stopped by the crossbar.Another attacking foray into the Paraguayan box resulted in a defender touching the ball with his hand, but the referee deemed it unintentional and the South Americans earned a temporary reprieve.With Bafana employing Tshepo Masilela and Bryce Moon effectively on the flanks, along with a smoothly operating midfield, SA’s ability to use the width of the field meant they were able to penetrate the Paraguayan defences.A cross from Moon found McCarthy in a good position, but his shot flew harmlessly over the goals with only the goalie to beat.The Paraguayans were struck a blow when they lost one of their stars, striker Roque Santa Cruz, after 21 minutes when he was injured in a poor challenge by his Blackburn Rovers’ teammate Aaron Mokoena.Stunning goalAfter half-an-hour, Masilela helped create the opening goal. Breaking infield, he burst into the penalty area before sending a hard cross across the goals to Surprise Moriri. With considerable skill, he trapped the ball with his chest and before it hit the ground volleyed a stunning shot into the top of the net past Villar.Two minutes into the second half McCarthy scored his record-breaking goal. Masilela crossed accurately from the left and despite the attentions of two defenders, the striker rose high and headed into the corner to the left of the keeper.Fifteen minutes later, Simphiwe Tshabalala put an exclamation mark on the scoreline by scoring South Africa’s third goal, thanks to a combination of superb finishing and vision.Killer blowAbout 20 metres out from the Paraguayan goal and on the left of midfield, he exchanged a one-two with McCarthy. After receiving the return pass, he, without hesitation, struck a superb chip over Villar, who wasn’t that far off his line. It was a beautifully-executed killer blow.Paraguay tried hard to find a reply, but SA goalkeeper Itumeleng Khune didn’t have much to do to keep a clean sheet. With South Africa in charge in the midfield, the momentum was on the side of Bafana Bafana.The 3-0 scoreline, while very unexpected, was thoroughly deserved. It not only gave South Africa a win over a highly-ranked opponent, but it also raised hopes that Bafana Bafana could indeed become a tough team to deal with by the time the 2010 World Cup arrives. Want to use this article in your publication or on your website?See: Using SAinfo material