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The latest round of national rail strikes are getting under way, with only 20% of train journeys expected to go ahead on Wednesday.
Some 40,000 RMT union members at Network Rail and 14 train companies are walking out over pay, jobs and terms.
The Department for Transport said the RMT was "hell-bent on creating further misery for passengers across the UK".
But the RMT accused Transport Secretary Grant Shapps of not allowing the rail industry to do a deal with the union.
Andrew Haines, Network Rail chief executive, said despite its best efforts to find a breakthrough there would be more rail disruption due to strikes.
In addition to the members of the RMT, members of the Transport Salaried Staffs' Association (TSSA) at Avanti West Coast, which operates some trains to Birmingham, are also going on strike on Wednesday.
The knock-on effects of the disruption are expected to roll in to Thursday, Network Rail said.
Separately, on Saturday, about 5,500 members of the train drivers' union Aslef at seven rail companies will strike.
Further RMT strikes are also planned for 18 and 20 August, with London Underground staff planning to strike on 19 August.
The Prime Minister's official spokesman had urged the RMT union to call off the strikes, saying on Tuesday: "We are concerned about the impact this will have on the public going about their everyday lives."
Places including Blackpool, Portsmouth and Bournemouth have no train services at all and elsewhere people are being told only to travel by train if necessary.
Network Rail has published a special timetable for Wednesday, with trains set to start later and finish earlier than usual, between 07:00 and 18:30 BST.
Passengers are being warned that the last trains from London will leave for Edinburgh at 14:00, for Birmingham at 15:43 and Manchester at 15:40.
'I booked my match tickets months ago'
The strikes are disrupting travel to the Women's Euro 2022 semi-final between Germany and France in Milton Keynes.
Thomas De Fraye from north London was looking forward to jumping on the train after work and heading to the match - but now there is no train.
He does not drive and a bus would not get him there in time for kick-off.
"I booked my tickets many months ago, before there was any news about strikes," said the 37-year-old. "I live in Enfield so it's not even that far so I was going to go after work.
"Now there are no trains running and an Uber would cost me £90 one way. That price would surely increase on the day due to demand and I have to get back too."
Mr De Fraye gave his ticket away on Twitter. "If I can help someone else go there that makes me happy," he said.
At loggerheads
"I can only apologise for the impact this pointless strike will have on passengers, especially those travelling for holidays or attending events such as the Uefa Women's Euro 2022 semi-final and the opening ceremony of the Commonwealth Games (on Thursday)," said Network Rail's Andrew Haines.
"It is frustrating to yet again ask our passengers to change their plans and only make essential journeys."
Network Rail says its latest pay offer is worth more than 5%, but that it depended on workers accepting "modernising reforms". However, the RMT union says this is a "paltry sum" and represents "a real terms pay cut".
RMT general secretary Mick Lynch said: "The Department for Transport controls the 14 train operators we are in dispute with and Network Rail is a publicly owned company who does not have the final sign off on any deal. That lies with the Secretary of State for Transport.
"We will continue to talk to the employers but there remains a huge chasm between us around pay, job security and working conditions."
A Department for Transport spokesperson said: "RMT's actions will affect people in need of urgent care, hardworking families off on long-awaited holidays and day trips, and businesses."
'It's a joke'
Student Blessing-Nicole Yanda from Watford was due to get the train to Birmingham City University to give a presentation as part of her digital marketing degree.
Now she cannot get there and has added it to the list of lectures missed due to the first round of strikes in June.
"The uni have said that although I can present online, there is nothing they can do regarding my attendance record," she said.
Miss Yanda, 19, is on a fast-track course that continues through the summer but she had to leave her student accommodation as it is used for the Commonwealth Games. She moved home to Watford as she also performs gigs in London to earn money while she studies.
"I rely on the train heavily as all my performances are in London. It's only an hour between Birmingham and London so I can travel between the two.
"It's so expensive getting on the train even with a student rail card. I spend £100 a week easily in a week, it's a joke.
"Rail workers get so much money and it's affecting other people's lives who can't get to work because of the strikes."
It's already turned into an unhappy summer on the railway.
This is the fourth day of national RMT strikes within 5 weeks.
Without a significant breakthrough in talks, more will follow next month.
Right now, it's hard to envisage that breakthrough happening soon - although all sides say they want to keep talking.
Negotiations between the RMT and Network Rail appeared to have made progress, before a stalemate emerged.
Things haven't even got to a pay offer with train companies - who say reforms need to be agreed first.
And other transport unions have industrial action in the diary too.
Many people can now work from home, meaning strikes don't affect commuters in the same way they used to.
But especially in the summer holidays, plenty of people will find their leisure plans disrupted - or find themselves forced to drive at a time when fuel prices are still high.
There are other effects too, including concern among some rail freight businesses that customers will be put off moving goods off the roads and onto the rails.
Train companies and the government also argue strikes could drive people away from the railway for good, depriving it of more revenue
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