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Around the stadium, images of flying birds were superimposed by digital trickery on the multitudinous throng. The sound was massive. On stage, Pink Floyd’s Nick Mason played drums and Mike Rutherford from Genesis played guitar, wearing a cool black suit, white shirt and rock star shades. Only the singer seemed to have missed the memo that this was a pretty grand event.

He wore a pink hoodie, trainers and jeans, and looked like he’d just got off a No 37 bus after a day’s busking on Clapham Common. Moon faced, unshaven, pale and ginger haired, playing a half size guitar, he was nobody’s idea of a rock hero. He was too ordinary, too inconsequential, too much your bouncy kid brother.

Millions of the global audience must have gazed at Ed Sheeran and thought: is this the best that British music has to offer? This guy? But even the doubters may have noted the ambition that shone in his bright eyes, the confidence he radiated in this terrifying arena, and the husky beauty of his voice. They probably wondered how far he’d go.

Reasons why Ed Sheeran is not boring

He was 21 then. Now he’s 23, and they have their answer. He’s the most listened to act in the world, according to Spotify his 860 million downloads politely shouldering Eminem and Coldplay into second and third place. He’s the biggest selling pop artist in the UK this year. This week his second album X (it’s supposed to mean “multiply” rather than “X rated”) hit a million sales and has just been nominated for a Grammy. He has three singles in the top 40. And he’s just announced that, as part of his tour next year, he’s going to play three nights at Wembley Stadium. By himself.

Sheeran’s image, his fans will tell you, is that he has no image, that he’s just a nice guy, a musician first and everything else way behind. And he certainly plays up his ordinariness. On Tuesday afternoon, he tweeted his 11.3 million followers: “Doing the Victoria secrets [sic] fashion show tonight and I’m eating a Greggs sausage roll in the dressing room.” After he sang on the catwalk, the tabloids gleefully recorded his repertoire of goofy grins, as a procession of statuesque models in jewel studded Fantasy bras strode past him. But outside, speaking to journalists, he displayed an intelligent wit. Asked if he thought he was a sex symbol, he said: “I don’t think a man can be sexy. I think a man can be gruff, or waxed and I’m neither.”

His philosophy is simple: “People say, ‘This is my favourite song. You should write another song like that.’ At the end of the day, fuck them. Be selfish. Why bother to please everyone? Please yourself. The rest will follow.” But he’s built a career on inclusivity. His music is a hybrid of acoustic folk, hip hop beat and rapper style lyrics, though his words are chatty and confessional rather than combative and sexist. His look, his clothes, his Little Taylor guitar, his one man band ism all express a romantic troubadour individualism that’s aching to connect with others. He accretes people like a magnet: fans, girlfriends, peer pop stars, glamorous producers like Pharrell Williams, dangerous rappers like The Game (with whom he used to smoke weed, before, of course, giving up.)

The most popular act on Spotify is a red haired 23 year old from Hebden Bridge (Illustration by Lauren Crow)

The key to his appeal is friendship. His most high profile pal is Taylor Swift, the world conquering pop/country singer with whom he spent half of 2013 on her US tour. Though the chemistry between them is plain, Sheeran has always said they weren’t lovers, just mutually admiring friends. It’s so romantic. He’s friends with Harry Styles of One Direction (an ex of Swift’s) for whom Ed has written songs. But away from the boy band circuit, he’s accepted by the hip hop fraternity. And lonely teens from Wales to Wyoming look at Sheeran and think: now there’s a pop star who I could go for a drink with without hating him.

Edward Christopher Sheeran was born in Hebden Bridge, West Yorkshire, in February 1991. His grandparents, Bill and Anne, came from Ireland. When Bill was training in dentistry at Guy’s Hospital, he once boxed Charlie Kray, elder brother of Ronnie and Reggie, to a standstill. He sang in the Catholic church choir at four, started guitar around the same age, and wrote songs in high school. He listened avidly to Van Morrison (whose younger self he strongly resembles) and went to his first concert at 11. He recorded his first songs at 14, dropped out of school at 16 and headed for London. There, he became a guitar technician for a two piece folk band called Nizlopi, and in due course opened their gigs with his songs. There followed a year of restless, night by night concerts 312 of them in 2009 and cautious recordings of songs on the “extended play” format.

His breakthrough year was 2010. He flew to LA to seek his fortune and played open mic nights across the city. In Jamie Foxx’s club, he was spotted by the owner, who offered him a bed and the use of his recording studio. Rather than seek a record company, Sheeran backed into the limelight, appearing on YouTube, bringing out more EPs, holding a free concert at the Barfly in Camden Town, to which 1,000 people turned up.

Ed Sheeran hanging out with famous friend Taylor Swift (Getty Images)

On Jools Holland’s BBC2 show, Later, he debuted a tender rap song called “The A Team” about a junkie hooker. Released as a download, it sold 58,000 copies in a week and became the year’s top debut single (and the eighth best overall.) At the Brits in 2012, Sheeran won both the Best British Solo Male Artist and British Breakthrough Act of the year. At the Ivor Novello awards, “The A Team” eclipsed Adele’s “Rolling in the Deep” and “Shake It Out” by Florence and the Machine to win “Best Song Lyrically and Musically”.

Sheeran was unstoppable. That summer he didn’t just close the Olympics, he also sang at the Queen’s Diamond Jubilee celebrations. Meanwhile, his first album + (as in “plus”) was released to mixed critical reviews but hit the top of the charts anyway. By March 2012, it had sold a million copies and charted in Australia, New Zealand, Ireland, Netherlands, Belgium and Switzerland.

After his year in the US with Swift, he returned to England to release his second album. The first single, “Sing!”, was a hit, and was taken up by Marks Spencer for a television commercial. In October, the video of a second song, “Thinking Out Loud”, featured a slimmed down, waistcoated Sheeran dancing a very creditable (and sexy) pas de deux with Brittany Cherry from the American So You Think You Can Dance talent show.

It represents a sea change in Sheeran’s style. He lost 35lb for the dance video, mainly by giving up beer. He’s given away most of his hoodies to charity, and now favours three piece suits. After playing a field of female admirers, he’s had a steady girlfriend, Athina Andrelos, for nine months. And he’s bought a farm in his childhood town of Framlingham, waiting to be renovated as a family home.

After a hectic career as everyone’s pal, he’s behaving like a proper grown up but one who’s still scheduled to play three concerts, at Wembley Stadium next July, solo, to a quarter of a million of his closest friends.

A life in briefBorn: 17 February 1991, Hebden Bridge, Yorkshire. A year later, his debut album, +, was a million seller within months. In 2012, he sang at the Olympics closing ceremony. In June 2014 he released his second album, X, which yesterday was nominated for a Grammy award.

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HomeNewsUK NewsDaniel Pelka trialDaniel Pelka trial: Boy killed by stepdad after wetting himself, mother tells courtGiving evidence in her murder trial, she told the court she did not call for help because she feared going to jail07:50, 16 JUL 2013Victim: Daniel Pelka (Image: PA) Get daily updates directly to your inbox+ SubscribeThank you for subscribing!Could not subscribe, try again laterInvalid EmailA boy of four was killed by his furious stepdad after wetting himself, his mother told a court today.Magdalena Luczak, 27, said boyfriend Mariusz Krezolek hit Daniel Pelka twice in the head after deliberately starving him for months.The 27 year old told Birmingham Crown Court she tried to stop the beating but was choked by Daniel’s step dad until she passed out.Luczak admitted she then left her unconscious son in a bedroom in the family home for more than 30 hours until he died in March last year.Giving evidence in her murder trial, she told the court she did not call for help because she feared going to jail.Jurors have been told starving Daniel resembled a Nazi concentration camp victim following a campaign of “incomprehensible cruelty”.Prosecutors claim he was deliberately starved, force fed salt and locked in a home made prison over a six month period.They said starving Daniel who weighed just 10.7kg at the time of his death died from a brain injury after being attacked.Luczak, wearing a green flowery top, blue trousers and trainers, gave evidence in both English and Polish with the help of an interpreter.She told jurors how she saw Krezolek, who she met in 2009, attacked Daniel after he wet himself in an upstairs bedroom.”I was in the living room and heard some screams,” she said. “Mariusz was shouting at Daniel in our bedroom because he wet himself.”Daniel was crying. I told him, ‘He is in fear of you.’ Mariusz hit him in the back of his head and Daniel fell to the front of him.”He said he was ‘my fg son’ and I should take him back to his father in Poland.”When he hit him I started shouting at him. Then Mariusz started strangling me. He grabbed me by the neck and strangled me.”Mariusz grabbed Daniel by his shirt and took him to the bathroom and cleaned him.”Then he grabbed him and dragged him to the box room. Then he hit him again with a hand into his head and he knocked him down to the mattress.”I shouted at him to not hit him on his head. Because I was shouting he grabbed me by the neck to calm me down.”Luczak told jurors the next thing she remembered was waking up on the living room sofa and seeing Krezolek smoking a cigarette.
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Boy found wandering streets in Peppa Pig onesie and no socks is reunited with his familyThe child was found wandering the streets by himself wearing nothing but a Peppa Pig onesie in Belfast by mum Jade Fee, who called the police17:34, 19 NOV 2017Updated19:16, 19 NOV 2017Manor Street in Belfast, where the boy was found (Image: Google Streetview) Get daily updates directly to your inbox+ SubscribeThank you for subscribing!Could not subscribe, try again laterInvalid EmailA young boy who was found wandering the streets with no shoes or socks and dressed in a Peppa Pig onesie has been reunited with his family.Police issued an urgent appeal to find the child’s parents or guardian after he was found in Manor Street, Belfast, alone.He was thought to be between three to five years old but unable to talk to police officers to tell them his name.Police Service Northern Ireland tweeted this evening: “Folks thanks so much for your help, we are super pleased that our lost boy has been reunited with his family.”Hundreds were left concerned when the police urged his family to come forward.Jade Fee, who found the child in Manor Street, says he waved “hello” to her from across the road.Teenager driven to suicide after vile abuse by boyfriend will become face of domestic violence campaignShe added: “Could my friends please share this so his mum can find him.”In a message posted to Twitter, Sgt W from nearby Tennent Street Police Station.”A resident of Lower Oldpark found a small missing boy in the street. He is believed to be around three to four years old with blond hair, wearing a green Peppa Pig onesie with no socks or footwear.”At this stage the child is with my LPT colleagues at Tennent Street Police Station and he is safe and well.”Unfortunately the little boy hasn’t been able to talk to us so he can’t tell us his name or other information.”Police Service Northern Ireland urged for people with information to come forward on Twitter,They wrote: “Folks we have found a 3 yr old boy in a green peppa pig onesy in Manor St Belfast.TeachersLecturer slammed after getting down on her knees and demonstrating on student how to put condom on with your mouthThe lecturer was filmed putting a condom onto a plastic penis being held by a shell shocked student in BrazilGun crimeHeartbreaking hospital picture of eight month old baby shot in the leg and arm with 30 pelletsBaby John Doyle was hit with a hail of pellets as his family put up a Christmas tree at their home in DublinCourt caseSchoolboy is ‘beaten by Pakistani men for dating a girl from their family who told him “Don’t mess with our blood”‘The Bengali student was taken prisoner by the Pakistani girl’s uncle, before her father, brother and cousin all joined in the attack, a court heardTeachersLecturer slammed after getting down on her knees and demonstrating on student how to put condom on with your mouthThe lecturer was filmed putting a condom onto a plastic penis being held by a shell shocked student in BrazilGun crimeHeartbreaking hospital picture of eight month old baby shot in the leg and arm with 30 pelletsBaby John Doyle was hit with a hail of pellets as his family put up a Christmas tree at their home in Dublin
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A 14 year old thug, who cannot be named for legal reasons, has admitted assault after footage of the “degrading” incident was viewed over 50,000 times.

The victim, who is aged 17, can be heard asking “Have I done anything?” after he was chased by a gang of youths.

The 14 year old bully says: “Get on your fing knees. Touch him I’ll bang you.

“No, don’t speak to him, kiss his shoe. Now. Kiss his fing shoe.”

“Do you want a broken jaw? Do you want a broken jaw? Get on your fing knees and kiss his shoe. Kiss his shoe now.

“Kiss his fing shoe. P. Fk you.”

He also spits on the victim as he lays helpless on the floor.

Police were alerted after the footage went viral and two boys aged 14 and 13 were arrested.

The older youth admitted carrying out the attack only hours after he had appeared at Swindon Youth Court on a charge of thieving from his sister.

Kate Prince, prosecuting,
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told the court the victim had been walking home from an ice skating session at the Link Centre, Swindon, Wilts.

The victim heard the voice of the defendant shouting “get back here” at which point he started running.

He ran out of breath and was quickly surrounded by seven youths when the video recording began.

Ms Prince added: “As a result the victim is scared to leave the house and worries about answering the phone.

“He feels belittled and small about being forced to kiss the boy’s shoe.”

Wayne Hardy, defending the 14 year old, said: “These offences happen the same day of being put on a referral order for theft in relation to his sister’s television.

“He is only 14, which comes as a surprise given his relative size. He says this happened because he was protecting his co accused, and bravado took over.

“His offending only started a few months ago, and he has amassed four serious convictions in that time.”

A member of the youth offending team told the court: “This is a worrying escalation. It is nasty bullying with degradation.”

The 14 year old will be sentenced on June 30.

A 13 year old from Swindon, has been charged with common assault and a public order offence and will appear in youth court on June 23.

Gun crimeHeartbreaking hospital picture of eight month old baby shot in the leg and arm with 30 pelletsBaby John Doyle was hit with a hail of pellets as his family put up a Christmas tree at their home in Dublin
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Boy BANNED from classes for wearing trainers when his shoes got soaked with snow unless he spends time in isolationFran Thomsen went into school in trainers after his school shoes were still wet from the previous day’s snow10:31, 5 DEC 2017Updated11:46, 5 DEC 2017Fran’s mum, Rachael, sent her son into school wearing trainers after his shoes got soaked with snow (Image: Grimsby Telegraph/BPM MEDIA) Get daily updates directly to your inbox+ SubscribeThank you for subscribing!Could not subscribe, try again laterInvalid EmailA teenage boy has been banned from classes for wearing a pair of trainers when his school shoes got soaked with snow unless he spends a day in isolation.Fran Thomsen, a student at Oasis Academy Wintringham, in Grimsby, went to school in trainers last Friday after his school shoes didn’t dry from the previous day’s snow.His parents decided to bring him home after he was placed in isolation for breaking the school uniform policy.But the school recorded that as ‘truancy’, and Fran has now been told he can’t return to class until he’s completed a day in isolation as a result,
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reports the Grimsby Telegraph.Mum Rachael said: “My son on Thursday got his shoes wet through because of the snow, and so he came home with soaking wet shoes.”We weren’t able to dry them properly overnight, so I said to him ‘just wear your trainers and if there’s a problem get the school to call me’.”Later on Friday, the school called to say he’d be spending the day in isolation for inappropriate footwear.”The school offered 14 year old Fran a pair of spare school shoes to wear for the day so he didn’t have to miss his lessons, but he refused due to his mum’s concern about using shared shoes.She said: “I’ve told him he’s not allowed to wear other people’s shoes because it’s just infection control.”I’m not prepared to put him in other people’s shoes we don’t know who’s owned them or where they’re from. I think it’s disgusting.”Rachael decided to bring her son home after he was placed in isolation as she wasn’t prepared for him to be punished for something outside his control.”The school have said he has to spend a day in isolation before he can go back to class I’m not prepared for my son to be punished for something that’s out of his control.”I didn’t have any alternative school shoes for him to wear I feel we have been treated unfairly.””Until the school back down I’m going to have to find my son an alternative place for his education.”Oasis Academy Wintringham state on their website that students should wear “black low heeled smart shoes”, and that trainers, black pumps, canvas shoes, ballet style shoes, and Converse shoes are not permitted.A spokesperson for the school said: “Oasis Academy Wintringham have long established rules regarding uniform. If ever our students do not have the appropriate uniform, they are offered suitable loan items from the Academy so that they can immediately return to their class.
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CCTV shoes the boy being led through the shopping centre (Picture:Pear)

A dad saved his sonfrom a suspected human trafficking gang after he spotted the boy in a shopping mall nine months after he was abducted.

Chen Zhonghong saw six year old Cheng Jiafu being pulled along by three men at a site just 30 minutes away from where he was kidnapped in May last year.

Death of billionaire drug company owner and his wife treated as then dialled for police, who rushed to the scene and grabbed the trio before they could flee.

CCTV footage at the scene shows one of the group being forced off their motorbike as they attempt to run.

Little Cheng Jiafu was swiped by strangers fromMatang Village in Qingyuan, Guangdong,
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just two hours after his dad left home to go to work last year.

Little Cheng Jiafu was swiped by strangers fromMatang Village in Qingyuan, Guangdong, just two hours after his dad left home to go to work last year. (Picture: Weixin)
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He came up with his intensive cardio boxing inspired fitness method after injuring his eye in a boxing match, leading him to shift his career. In the early 2000s his Aerospace classes took off in New York City and attracted a ton of celebrity clients. Now he’s taken his methods to the West Coast.

Aerospace’s new West Hollywood location has sleek white walls, complimentary towels and a pristine white locker room. Newcomers are recommended to start with “Intro to Aerospace,” which is a high cardio class with shadow boxing (or punching in the air).

After an intro class,
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my arms burned from air punches and I became winded from jumping up and down; Aerospace coaches keep going long after you want to pause. A regular assured me that it gets a little easier with time. He said he comes with his teenage son, who can “get out of his head” and blow off some steam.

The boxing class is no solution to the world’s evils (or your own), but you can barely think as the challenging cardio leaves you gulping for air while you relish each swing,
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and the only thing to do is to keep moving.

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Canadian Olympic boxer Mike Strange of Niagara Falls dons giant golden boxing gloves with New Glasgow Mayor Barrie MacMillan at New Glasgow town hall Thursday morning. Strange is running 90 marathons in 90 days to raise funds for the McMaster Stem Cell and Cancer Research Institute and all Ronald McDonald Houses at sick children’s hospitals across Canada. JOHN BRANNEN THE NEWSThat’s the message he’s taking from St.

That’s 26.2 miles each day. For 90 days.

But this runner is up for a good fight. He represented Canada in three consecutive Summer Olympics and took home gold for Canada during the Commonwealth Games.

All proceeds from this run will go to the McMaster Stem Cell and Cancer Research Institute and to all Ronald McDonald Houses at sick children’s hospitals across Canada.

“It’s tough for families to take off work when their child is sick,” said Strange. “Imagine trying to carry on with your life while having so much more to worry about.”

His inspiration comes from Matthew (Matteo) Mancini whom he met in the fall of 2011.

“Such a brave young man, someone that you just wanted to be around.”

Matteo had just lost a leg to cancer but that did not stop him coming out on the first BoxRun in 2012. He passed away on May 8, 2013. Strange honoured him by starting this years BoxRun on May 8, 2014.

In New Glasgow,
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Mayor Barrie MacMillan, who gave him gifts on behalf of the town, greeted Strange.

His next stop is in Halifax where he’ll meet up with Mickey MacDonald at the famous Chicken Burger restaurant.

By the time he wraps up his run in Niagara Falls, he’ll have gone through eight pairs of sneakers.

“But if it helps the kids, it’s worth it,
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” Strange said.

Donations can be made on the Box Run homepage. More information on the run along with photos and updates can be found on the Box Run Facebook page and Twitter account.

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From the experiments performed by Takeuchi et al (1999) it was found that two genes of the T Box family, Tbx4 and Tbx5, are important factors in determining the identity of limb buds in chicks. It is believed that the differential expression of Tbx4 and Tbx5 in leg and wing buds, respectively, are the determining factors where expression of Tbx4 tells a limb bud to form toes, scales, and the typical leg skeletal pattern. On the other hand, the expression of the Tbx5 gene is prospective limbs influences the formation of wing characteristic digits, feathers, and skeletal pattern.

However, as Takeuchi et al (1999), Logan et al (1998), Gibson Brown et al (1998), and Rodriguez Esteban et al (1999) show, there is a complex series of signals leading up to, and continuing after, the expression of the T Box genes.

Figure 1. Genetic interactions involved in the expresion of the T Box genes in prospective limb fields. The top pathway depicts the series of events taking place in the forelimb leading to wing development, whereas the bottom pathway represents the events leading to leg development in the hindlimb, (Takeuchi et al 1999).

In contrast, Tbx5 was confined to the forelimb and is detected by stage 14 adjacent to somite 10 23. This pattern of expression is shifted to somites 11 24 by stage 15.

Experiments performed by Takeuchi et al (1999) show that when RCASBP Tbx5 EGFP or RCASBP Tbx4 EGFP (see methods)are electroporated into prospective limb fields, misexpression caused dramatic morphological changes. As it was observed, when Tbx5 was ectopically expressed in leg fields caused elongation of the fibula including articulation with the metatarsal bones whereas the fibula is normally short and articulation does not occur. In addition, three digits were formed, versus four in normal legs, and partial scale to feather conversion. Thus it is clear that ectopic expression of Tbx5 induces partial wing like morphology where a leg should normally form.

Figure 2. The effects of ectopically expressed Tbx5 in limb development. The red arrow in box D shows complete scale to feather conversion, whereas box E shows partial scale to feather conversion. Box F shows elongation and articulation of the fibula (red arrow) contrasted with a normal leg (box G), (Takeuchi et al 1999).

Similarly when Tbx4 was introduced to presumptive wing fields, a partial leg pattern was observed with four toe like structures, complete with claws and feather to scale conversion. In addition, some skeletal deformations were observed, including thinning of the ulna.

Figure 3. The effects of ectopically expressed Tbx4 in limb development. The red arrow in box H shows complete feather to scale conversion. Box I shows four separate digits with claws, while box J shows the thin ulna along with the four complete digits, (Takeuchi et al 1999).

As described in the interactions page, the ectopic misexpression of one T Box gene utimately interferes with the expression of the other. Consequently, the observations of endogenous Tbx4 transcripts were down regulated as Tbx5 was ectopically introduced. On the other hand, Tbx4 cannot suppress endogenous Tbx5 expression thus demonstrating a hierarchy of sorts.

This phenomenon can be explained through the interpretations of experiments performed by Takeuchi et al (1999), Rodriguez Esteban et al (1999), and Johnson and Tabin (1997) involving the fibroblast growth factor 8 (FGF 8) induced extra limb system. When FGF 8 is expressed in prospective limb buds close to somite 21, extra wings developed, whereas ectopic FGF 8 close to somite 25 induced extra legs to develop. However, when FGF expressing cells were mixed with TBx4 producing cells and implanted at somite 21, endogenous transcripts were down regulated and Tbx4 transcripts were expressed throughout the limb bud, influencing structures to form as a leg would. As described later, expression of the Hox gene, Hoxc11, normally expressed only in legs, were normally observed.

Figure 4. The effects of ectopic FGF transplants on limb development. Ectopic expression of FGF alone give rise to extra wings (box G and H), whereas box I and J show the development of an extra leg when FGF is coupled with Tbx4 expression, (Rodriguez Esteban et al 1999).

Thus, a hierarchy of expression is theorized with Tbx4 acting as a major determinant of leg identity where leg development is a more likely result when Tbx4 is expressed early in development. In other words, Tbx4 can induce leg like morphology, even in wing destined limb fields, when expressed at the initial stages of limb development, whereas the influence in later stages is not as great and limb conversion is less likely.

The T Box genes are involved with a number of gene groups, including the Hox code and Pitx1. When Tbx5 is misexpressed in limb fields, wing specific Hoxd9 was clearly induced, coupled with repression of endogenous leg specific Hoxc9. Tbx4 has a contrasting effect where Hoxc9 was misexpressed in wings, with the normal Hoxd9 gene being down regulated.

The gene Pitx1 seems to have some interactive role with Tbx4 in achieving leg identity as the expression of Pitx1 was not affected in either misexpressed Tbx5 legs or Tbx4 wings. Pitx1 is seen normally in legs by stage 11, preceding the expression of the T box genes (stage 14 for both). The initial expression domain of Pitx1 is fairly broad, not being confined to the prospective leg fields, as is Tbx4, implyinga role in inducing Tbx4. Takuchi et al (1999) tested this hypothesis by implanting FGF producing cells at somite 23 and observing the sequential order of expression of genes. It turns out that Pitx1 is expressed and observed 6 hours after implantation, whereas the T Box genes are observed 12 hours later.

However, it was noticed that the Tbx4 being expressed was done so adjacent to the area of FGF producing cells, leaving a gap in the expression domains. This observation implies that the Pitx1 gene acts to regulate the TBx4 indirectly.

With regards to early limb development and the expression of the T Box genes, Gibson Brown et al (1998) observed the involvent of such with respect to the AER and ZPA. When leg mesenchyme cells were grafted beneath the AER of the wing bud, the misexpression of Tbx4 was observed. Similarly, when Tbx5 producing wing cells were grafted beneath the leg AER, Tbx5 gene transcripts were clearly observed.

Interestingly, when the AER was removed in developing wing and leg buds, the expression of Tbx5 and Tbx4, respectivley, were maintained. Thus, the maintenance of the T Box genes, once established, are not dependent of the continuation of the AER/ZPA derived signals.

It has been discovered that mutations in the Tbx5 gene are responsible for causing human diseases such as the Holt Oram Syndrome (Gibson Brown et al 1998 and Logan et al 1998), affecting the development of the fore limb. The Holt Oram Syndrome is characterized by a reduction in the radius and loss of the thumb. As it is, there are no phenotypic diseases or deformations known yet, caused by mutations involving the Tbx4 gene.

In conclusion, the role of the Tbx4 and Tbx5 gene is clearly that of an important one in the identification process of limb buds. It shows that the T Box genes regulate the expression of some downstream targets that influence the formation of structures that are directly related to the specific T Box gene being expressed. In other words, Tbx5 and Tbx4 induce downstream factors to follow a pathway that makes wing like structures in Tbx5 expressing limbs versus leg like structures in Tbx4 expressing limbs.
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Ms Skipper said: “The hospital said she’s going to have to have an HIV test in three months’ time. She’s had blood tests and a hepatitis injection and she’ll have to have more, but it’s the wait to find out if she has something worse that’s so terrifying for us.”

Ms Skipper and Macie’s father Kenny Parker had taken Macie, her twin sister Madison, and the girls’ cousin Cameron, five, to the bowling alley on Friday night.

“I said, what are you doing?’ and she said,
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Mummy, I hurt my arm.’ “I was crying my eyes out and the manager ran over and asked if I was OK and I said, no, not really, my daughter’s found a syringe on the floor and thinks it stuck in her arm.’ “The manager took us into the office where there was better light to check her out,and a security guard said it looked like she had two holes in her arm.

“It looked like it went in sideways so they immediately called an ambulance because they were worried heroin could have got into her bloodstream.

“Macie was just sitting there holding her arm. She didn’t have a clue what was going on.

“This is a kids’ place it’s a place where children have parties. My daughters love it.

“You just don’t think there’d be something like that there.

It’s a place where children should feel safe.

“Macie seems fine now. We didn’t get in until 2am but she just wanted to see her sister, to be honest. They’re never apart.

She just kept saying she had a poorly arm.

“It was an insulin needle but the hospital turned around and said these needles can be used for anything and that an insulin user would know to put it in a bag or a bin.”
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