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Researchers publish how-to guide for mouse-human chimeric embryo

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In a bid to ‘fundamentally change how we treat many human diseases’, a new paper details how to grow human cells in a mouse embryo.

In a research paper published last week (2 July), researchers from the University of Buffalo gave a step-by-step guide to their biomedical research techniques involving mouse-human chimeras.

“This paper will enable many scientists to use this new platform to study the human disease of their interest,” said Dr Jian Feng, professor in the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo and senior author of the paper.

“These mice contain critical human cells, tissues or even organs so that they more accurately reflect the human condition.”

This isn’t the first time Feng has made headlines for his work. Published in Science Advances back in May 2020, Feng and colleagues caused a splash when they described their biomedical research concerning mouse-human chimeras.

This time, however, the researchers aren’t showing what they did, but describing how to do it.

In Greek mythology, a chimera was a fearsome, fire-breathing creature with aspects of a lion, goat and snake. Modern medical chimeras give a nod to antiquity and chimera now refers to organisms with cells from two or more sets of DNA.

In this case, the researcher chose that of a mouse and a human. The process involves human primed stem cells co-developing with the inner cell mass inside of a mouse embryo.

Creating chimeras containing 4pc human cells, they have taken a step forward for medical research that has struggled to keep these cells alive because of compatibility issues.

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The ability to mass-make mature human cells in a living organism is a central part of the predicted therapeutic potentials of stem cells.

This could involve creating human-like models using chimeras for research, or the generation of human tissue in animals.

So impressed was the scientific community after the publication of this research, the authors were invited to share their methods in Nature Protocols and facilitate the research of others.

“With our method, the human cells are made along with the mouse during the development of the mouse embryo. There would be better matching and no rejections, because there are ways for the human cells to be made where there is no competition from their mouse counterparts,” Feng explained.

“If naive human pluripotent stem cells are able to generate significant amounts of mature human cells in other larger species, it could be possible to make human tissues or even human organs in chimeric animals.”

Research on chimeras has faced criticism in the past, arising from bioethical concerns. Many researchers fall on either side of the debate.

Feng highlighted the critical problem of organ shortages, however, and argued: “Ultimately, a better understanding of how human cells develop and grow in chimeras may enable the generation of human cells, tissues and organs in a completely artificial system and fundamentally change how we treat many human diseases.

“Research using chimeras is a bridge that must be crossed to reach that possibility.”

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An Cosán wants to help tackle the digital skills gap with suite of new tools

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The CEO of the non-profit told attendees at a community webinar that almost one in two adults in Ireland has low digital literacy levels.

Dublin-based education non-profit An Cosán is introducing a new suite of digital tools in an effort to tackle Ireland’s digital skills shortage.

Several An Cosán team members addressed the issue and the centre’s plan to tackle it at a recent webinar on digital inclusion the organisation hosted for its community partners.

Heydi Foster, CEO of the non-profit, called for a “whole of society approach” to increasing digital literacy, which, she said is an essential requirement to participate fully in society and to thrive in the 21st century.

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Foster said: “Almost one in two adults in Ireland has low digital literacy levels, according to the Digital Economic and Society Index 2018. This is something that we all have a responsibility to address as a matter of urgency.”

She told the webinar attendees that a “collaboration between community, state and corporate sectors is urgently needed to ensure every adult has the necessary literacy, numeracy and digital skills to fully engage in society.”

Foster reminded the community partners of An Cosán’s founding principle “to leave no one behind” when it was first set up 35 years ago by co-founders Dr Ann Louise Gilligan and Dr Katherine Zappone.

The non-profit’s digital inclusion co-ordinator, Mark Kelly, then spoke about how An Cosán had been working with its partners to address digital exclusion in Ireland. Measures taken include a ‘Digital Stepping Stones’ tool developed with Accenture that allows people to evaluate their digital level competency. First rolled out in 2020, the tool identifies where people may need to upskill to fix any gaps in their digital skillset.

Kelly said the tool had been used by more than 5,300 people across the further education and training sector, including education and training boards, regional community training centres, local development companies, family resource centres and other community organisations.

To complement the success of the digital skills assessment tool, Kelly announced the development of a new suite of digital learning methods, using DigComp, the European digital competence framework.

Ariana Ball, corporate citizenship lead at Accenture, spoke during the webinar about the need for a growth mindset when it comes to teaching digital skills. The professional services company last year published a report on the digital skills shortage.

The report found that at least a quarter of the Irish population is excluded from an increasingly digital society because of socioeconomic reasons. This is leading to a “two-speed digital economy”, the report warned. It highlighted, in particular, the need for increased digital skills help for older people.

Recently, Vodafone Ireland partnered with charities Alone and Active Retirement Ireland to launch a new training programme to help those over the age 65 improve their digital skills. The Hi Digital programme aims to support 230,000 older Irish people as they overcome digital disenfranchisement.

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The death of Charles Babbage, mathematician and inventor – archive, 1871 | Computing

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The death is announced of Mr Charles Babbage, who has long held high rank among the mathematicians of the day. He was born on 26 December 1792, and having been privately educated, proceeded to Trinity College, Cambridge where he took his BA degree in 1814; but, curiously enough, his name does not appear in the mathematical tripos. In the course of his mathematical studies he found fault with the logarithmic tables then in use as being defective and unfaithful; and in order to improve them visited the various centres of machine labour in England and on the continent, and on his return directed the construction of a “difference engine” for the use of the government.

Another result of this tour was the production of his work on the Economy of Manufactures. By 1833 a portion of his machine (popularly known as “the calculating machine”) was prepared, and its operations were entirely successful. It was, however, never completed. He next prepared his Table of Logarithms of the Natural Numbers from 1 to 108,000, a work which was so highly esteemed that it was very soon afterwards translated into almost all the European languages.

A scaled-down version of Charles Babbage’s Analytical Engine, constructed in the 1860s.
A scaled-down version of Charles Babbage’s Analytical Engine, constructed in the 1860s. Photograph: Alamy Stock Photo

In 1811 Mr Babbage was elected Lucasian professor of mathematics, an office which had been filled by Sir Isaac Newton, Dr Isaac Barrow, Bishop Turton, Professor Airey, and other eminent persons. This post he resigned in 1811. Among his most prominent works may be mentioned A Ninth Bridgewater Treatise, the design of which was to show the error of a supposition implied in the first volume of that celebrated series, that ardent devotion to mathematical studies is unfavourable to religious faith.

Mr Babbage once, and it is believed once only, sought political honours, having become in 1832 a candidate for the borough of Finsbury, in the advanced Liberal interest, but was not successful. He was a Fellow of the Royal Society and a member of a large number of literary institutions.

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How to keep a support contract • The Register

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On Call Let us take a little trip back to the days before the PC, when terminals ruled supreme, to find that the more things change the more they stay the same. Welcome to On Call.

Today’s story comes from “Keith” (not his name) and concerns the rage of a user whose expensive terminal would crash once a day, pretty much at the same time.

The terminal in question was a TAB 132/15. It was an impressive bit of kit for the time and was capable of displaying 132 characters of crisp, green text on a 15-inch CRT housed in a futuristic plastic case. Luxury for sure, unless one was the financial trader trying to use the device.

Once a day, at around 13:30, the terminal would hang. The user would have to reach behind it, power it off, wait a bit, and then fire it back up again. To placate the angry customer, a replacement was dispatched, and all was well. Until the problem started again. Another replacement was made. Another week or so went by with no complaints. And again, another call: the terminal was hanging. Same time. A few times a week.

“These terminals were in the thousand-dollar range,” Keith told us, so a monthly replacement cycle was not really an option. He even used one of the faulty units himself for a while and encountered no issues, which was odd in itself and, we reckon, planted a seed of suspicion.

As for the customer, he was raging by this point. “He was threatening to cancel our contract for his entire firm,” remembered Keith, which would hit the bottom line hard. A salesperson was sent out to see what was happening, but there was no failure.

A technician went out; again no failure. Was this a case of “Technician Syndrome”, where a problem cannot be replicated in front of service personnel? Maybe. Keith’s team were at their wit’s end while the customer had hit the end of his tether and gone beyond.

The solution to the problem was accidental. Keith was back on site, diagnosing an unrelated software issue, but could see the suspect terminal on the other side of the room. As he watched, the trader using the machine sat back for lunch, flipping through the pages of a financial newspaper. A phone call came through, and the trader slung the paper on top of the monitor, took the call, and then resumed work.

Oblivious to the newspaper.

A few minutes later there was uproar. The trader had stood and was slapping the side of the terminal, yelling all manner of not-safe-for-work oaths and casting aspersions upon the good name of Keith’s firm, the software, the programmers, and the computing industry in general. The cursing continued as the trader reached behind for the power switch, knocking the paper aside.

Keith had his solution. But was smart enough to know that a bland presentation of facts would probably not help. Instead, he arranged for his office to call the trader and tell him that a tech was on the way to help. He waited until the trader was distracted and sauntered over.

“Sure enough,” said Keith, “he said he was glad to see me but launched into a tirade again about the device’s many faults.”

He let the customer vent for a while, and surreptitiously placed the newspaper back on top over the heat vents on the terminal while pretending to examine the rear of the unit.

Now patience was needed. It wouldn’t take long – the terminal had, after all, only just recovered from its last overheating episode – and Keith encouraged the trader to unload all his woes and grievances.

The bug list was building as the screen suddenly flickered and locked up. “There! You see that?” exclaimed the user. Keith nodded and reached round the side of the terminal to cycle the power. Sure enough, it came back up.

Keith made a show of thanking the user for showing him the elusive bug and was staging a call with a co-worker, supposedly to prepare a replacement, when the terminal locked up again.

Keith wrinkled his forehead at the “mystery” before offering up an explanation.

“Ah!” he exclaimed, “Did you see how that flicker started from the top and moved to the down?”

Those familiar with the technology will know it was just following the raster pattern. The customer, on the other hand, did not.

“That is often a sign it is overheating,” said Keith, playing fast and loose with the truth, “but this office is cool?”

He pretended to be mystified until the penny dropped for the trader, who unleashed yet more expletives as he realised where he’d dropped his newspaper and snatched it away from the vents.

Feeling the volcanic heat spewing from the depths of the terminal, he turned to Keith, suddenly concerned: “Will it be OK?”

Of course it would. It had only been overheating for a short time every day. The apologies from the customer, who had “discovered” the problem, were profuse and copious. Keith excused himself, but not before rubbing a bit more salt into the wound by telling the user he needed to cancel the burn-in process of yet another expensive replacement.

As it turned out, rather than the customer cancelling the support contact, it ended up being extended.

“It was a good thing I’d let him ‘discover’ the fault,” said Keith. “If I had found it, he would have been very defensive and we still might have lost that contract.”

The minor bugs the user had reported while Keith had been waiting for the overheating to happen again were swiftly dealt with and the enhancement requests logged. Keith also reported back to his boss, who spent rather a lot of time laughing.

“It was a good day.”

Ever set the stage so the customer thinks they’re the hero of the hour? Or maybe you’ve wished all manner of unpleasantness upon your suppliers before realising the blame laid with you all along? Tell us about the time you picked up the phone with an email to On Call. ®

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