Engineered mini-kidneys come of age A glomerulus-on-a-chip could model patient-specific kidney diseases, guide therapeutic discovery Related Growing organoids under flow increases their potential for drug testing, regenerative medicine Human stem cells model the kidney’s filtration barrier Every day our kidneys tackle the daunting task of continuously cleaning our blood to prevent waste, salt, and excess fluid from building up inside our bodies. To achieve this, the kidneys’ approximately 1 million minute filtration units, called glomeruli, first remove both waste products and precious nutrients from the bloodstream. Then, specialized structures known as the proximal tubules reabsorb the “good” molecules — glucose, amino acids, some vitamins, and electrolytes — returning them to the bloodstream.But the reabsorptive functions of the proximal tubules can be compromised by drugs, chemicals, and genetic and blood-borne diseases. Because our understanding of how these effects occur is still limited, researchers have been working to replicate proximal tubes and other kidney structures in the lab so they can better study their functions, screen drugs without testing on humans or animals, and ultimately use them as a foundation to engineer kidney replacements for diseased or damaged organs.To help study renal reabsorption, in 2016 Wyss Institute core faculty member Jennifer Lewis and her team — working within the institute’s 3D Organ Engineering Initiative, which she co-leads, and in collaboration with the Roche Innovation Center Basel in Switzerland — created a 3-D proximal tubule model in which fluids could be continuously streamed through the tubules.While that model removed molecules from the system, however, it lacked a functional blood-vessel compartment for picking up molecules again so they could be reabsorbed by the proximal tubules.This week, Lewis’ team has presented a solution to that problem: a 3-D vascularized proximal tubule model they created in which independently perfusable tubules and blood vessels are printed adjacent to each other within an engineered extracellular matrix. Their study is published in the Proceedings of the National Academy of Sciences (PNAS).“We construct these living renal devices in a few days and they can remain stable and functional for months,” said first author Neil Lin, a Roche Fellow and a postdoctoral fellow on Lewis’ team. These 3-D vascularized proximal tubules, Lin continued, demonstrate that the team’s multitissue constructs are indeed mature and functional. “[They] exhibit the desired epithelial and endothelial cell morphologies and luminal architectures, as well as the expression and correct localization of key structural and transport proteins and factors that allow the tubular and vascular compartments to communicate with each other,” he said.,As a first step toward testing drugs and modeling diseases, the team induced hyperglycemia, a high-glucose condition typical of diabetes and a known risk factor for vascular disease, into their model by circulating a fourfold-higher-than-normal glucose concentration through the proximal tubule compartment. “We found that high levels of glucose transported to endothelial cells in the vascular compartment caused cell damage,” said Kimberly Homan, a co-author of the study and a research associate in Lewis’ group at the Wyss Institute and the Harvard John A. Paulson School of Engineering and Applied Science (SEAS). “By circulating a drug through the tubule that specifically inhibits a major glucose transporter in proximal tubule epithelial cells, we prevented those harmful changes from happening to the endothelial cells in the adjacent vessels.”The team’s immediate focus is to further scale up their new model for use in pharmaceutical applications. “Our system could enable the screening of focused drug libraries for renal toxicity and thus help reduce animal experiments,” said Annie Moisan, a co-author and industry collaborator on the study, and principal scientist at Roche Innovation Center Basel. “I am thrilled by the continued efforts from us and others to increase the physiological relevance of such models, for example by incorporating patient-specific and diseased cells, since personalized efficacy and safety are the ultimate goals of predicting clinical responses to drugs.”“Our new 3-D kidney model is an exciting advance, as it more fully recapitulates the proximal tubule segments found in native kidney tissue,” said Lewis, who is also the Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS, the Jianmin Yu Professor of Arts and Sciences, and a member of the Harvard Stem Cell Institute. “Beyond its immediate applications for drug screening and disease modelling, we are also exploring whether these living devices can be used to augment kidney dialysis.” Currently, life-saving dialysis machines filter blood, but they are unable to retrieve from the filtrate the nutrients and other molecules that the body needs for many of its functions, which can cause specific deficiencies and complications down the line. Lewis and her colleagues believe that 3-D bioprinted vascularized tubules may lead to improved renal replacement therapies.“This study presents a significant step forward in human kidney engineering that enables human disease and drug-related studies to be carried out over extended periods of time in vitro,” said Wyss Institute Founding Director Donald Ingber, who is also a professor of bioengineering at SEAS and the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital. “It also represents a major step forward for the Wyss Institute’s 3D Organ Engineering Initiative, which aims to generate functional organ replacements with enhanced functionalities for patients in need.”The study was also authored by present and past members of Lewis’ team Sanlin Robinson, David Kolesky, and Nathan Duarte. It was funded by grants from the National Institutes of Health, Harvard’s Wyss Institute for Biologically Inspired Engineering, a Roche Postdoctoral Fellowship, and a donation from the GETTYLAB.
Liverpool boss Klopp confident over Keita injuryby Paul Vegas10 months agoSend to a friendShare the loveLiverpool boss Jurgen Klopp is confident Naby Keita’s injury suffered in victory over Wolves isn’t serious.Keita was forced off shortly before the hour mark at Molineux having picked up a couple of knocks.However, Klopp said post-match that Keita’s issues ‘should be good’.”Did you see it back the first two situations? Was it a penalty or not, because he had a proper cut on the foot and everyone said ‘diver!’, but you don’t get a cut from a dive I would say,” the boss stated, during his press conference.”Then he had another one on his ribs, so that’s obviously [why] it didn’t work out. But it should be good. Two things which are a bit painful but I don’t think will be a problem for him.” About the authorPaul VegasShare the loveHave your say
Chelsea legend Drogba happy Lampard backing young playersby Paul Vegasa month agoSend to a friendShare the loveChelsea legend Didier Drogba is happy seeing manager Frank Lampard backing the club’s young players.Drogba believes Lampard’s emphasis on selecting young players for first-team games in the top flight and Champions League will prove to be a success.He said, “I think he (Lampard) is focusing on Chelsea and it happens that he needs to work on young players, to give them a chance.”Being an ex-player from the club, it helps a lot because we’ve seen all these kids when we were training.”So, you know, you have to give them a chance and when you do, they deliver.”They’ve been performing. Of course, there will be maybe a lack of experience in big games like Champions League but I’m not worried.”I’m really happy with the work that Frank is doing right now. And the fans, and the people who know football, they understand.” About the authorPaul VegasShare the loveHave your say
AC Milan director Boban: Giampaolo sacking a defeatby Carlos Volcano13 days agoSend to a friendShare the loveAC Milan director Zvonimir Boban admits sacking Marco Giampaolo was a “defeat”.Giampaolo was axed and replaced by Stefano Pioli this week.Boban said, “Things are a bit difficult for Milan right now because sacking a Coach is a defeat. Marco’s a very good person and it’s a huge regret.“It was a unanimous decision, only and exclusively to improve Milan’s performances. If you see that you can’t push any further then you think about making a change.“I want the good of this club and I intend to bring them back to the levels of my Milan. We’re working on all fronts to make that happen soon.“Results don’t only depend on the Coach. There are players and directors. We’re all to blame.“To Marco, just after his arrival at Milanello, I said, ‘I hope to leave this city with you.’ I did the same with Paolo [Maldini], who I’m in the office with every day.“We need time and we’ve always said that. We never made any declarations. We’re the youngest team in Serie A. This is the case in every line of work.“We know what needs to be done, but it’s a process. We can’t say, ‘those phenomena Paolo and Zvone are there so winning is compulsory or for granted.’“We’ll do our best. Maybe in our third year we’ll see a better and more competitive team, a team who will try to play better and better with each day that passes.“If we’re a good team, we’ll understand certain things more than others, otherwise another team will succeed.“Certainly, football isn’t what it was in the old days.” TagsTransfersAbout the authorCarlos VolcanoShare the loveHave your say
After defeating Minnesota 40-35 Saturday night, Iowa is 10-0 and still has a chance to represent the Big Ten in the College Football Playoff. Naturally, Iowa City is buzzing with excitement. But not every resident in town is happy with the development.According to Iowa City’s daily activity log, a resident who lives just a few blocks away from Kinnick Stadium thought the stadium got too loud Saturday night. The caller wanted to talk to the police about the situation. Check it out:Want to know what over 110,000 fans in one stadium looks like? #HawkFanHeaven pic.twitter.com/UqBloaDrjs— University of Iowa (@uiowa) November 15, 2015Something tells me that the police didn’t do much about it. Iowa hosts Purdue this upcoming Saturday – whoever made the call might want to leave town temporarily.
Youth and Culture Minister, Hon. Lisa Hanna, is urging the nation’s two most influential stakeholders, women and musicians, to remain steadfast as positive influences both locally and globally, while dismissing issues detracting from this course.“Our mission, that must be accomplished, must transcend personal agendas for the upliftment of all our people. We must ridicule personal vengefulness and, at all times, we must ensure that we are our sisters’ and our brothers’ keepers,” the Minister asserts.She was addressing over 400 participants from some 30 nations at the closing ceremony for the International Women’s Forum World Cornerstone Conference, at the Montego Bay Convention Centre in Rose Hall, St. James, on May 31.[RELATED: Creative Expressions Can Unlock Wealth – PM]Noting the impact of Jamaica’s music globally, Ms. Hanna said the country’s musicians and its women must accept and understand that they are the “revolution and the transformation” and that, as a nation “we have the same empathy of purpose that gives us the same shared experiences’.“Our journey as a people has been blessed through a strength of purpose, that we are the founders of our own destiny. The music helped to create a momentum that drove political leaders to focus on the realities of people’s lives,” she pointed out.The Minister informed that through music, Jamaica advanced a wave of radicalism that confronted global powers in a manner that still befuddles many.“We were the first to boldly enter the halls of the United Nations and lobby against the Apartheid regime in South Africa. Emboldened by the music, we promoted democracy in Zimbabwe, and supported Fidel Castro in his revolution in Cuba and the Cuban involvement in the war in Angola,” she outlined.Ms. Hanna pointed out that as the world currently seeks to transition from a confrontational setting to more harmonious co-existence, “we in Jamaica are at a crossroads.”“Today, the reality is that we can transform the world in minutes … with vision. Our music is expected to be the platform on which the world will build its future generation of power. Today when you hear the music of Jamaica … you are not just listening to scintillating rhythmic combinations and melodies; our music is about mobilizing and in most instances, a call to action,” Ms. Hanna said.Contact: Glenis A. Rose
Companies in this story: (TSX:GSPTSE, TSX:CADUSD=X) The Canadian Press TORONTO — Canada’s main stock index fell in late-morning trading, weighed down by losses in the materials sector, while U.S. markets moved lower.The S&P/TSX composite index was down 16.26 points at 14,922.92.In New York, the Dow Jones industrial average was down 120.17 points at 23,875.78. The S&P 500 index was down 13.61 points at 2,582.65, while the Nasdaq composite was down 53.01 points at 6,918.47.The Canadian dollar traded for 75.38 cents US compared with an average of 75.42 cents US on Friday.The February crude contract was down 18 cents at US$51.41 per barrel and the February natural gas contract was up 37.7 cents at US$3.48 per mmBTU.The February gold contract was up US$1.10 at US$1,290.60 an ounce and the March copper contract was down 3.40 cents at US$2.63 a pound.
New Delhi: Passengers on the a Noida-bound train were deboarded on Wednesday at the Akshardham Metro station after a minor smoke incident was reported from the train’s last coach, DMRC officials said. The “minor” smoke was reported at the Pragati Maidan metro station. “No physical cause was observed by the maintenance staff but as a precaution, passengers were de-boarded at Akshardham Metro station,” a senior official of the Delhi Metro Rail Corporation (DMRC) said. “The train was thereafter withdrawn from the service and sent for investigation at Yamuna Bank depot,” the official added.
London: British MPs will on Wednesday hold votes on various Brexit options even as Prime Minister Theresa May comes under pressure to announce a departure plan to get support for her unpopular divorce deal. Three years after a referendum in which Britain voted to leave the European Union, the country is gripped by painful uncertainty over how — or even whether — it should put an end to its 46-year membership. May’s deal negotiated with Brussels has already been voted down overwhelmingly by parliament twice but the government is widely expected to present it for a third time on Thursday to ensure an orderly Brexit. Also Read – Saudi Crown Prince ‘snubbed’ Pak PM, recalled jet from USEU leaders said Britain could leave the EU on May 22 if the deal is adopted this week, or face a potential no-deal Brexit as early as April 12. In a bid to find Brexit alternatives, lawmakers took the unprecedented step on Monday of seizing control of Wednesday’s parliamentary business. MPs will hold a series of “indicative votes” — indicating their preferences on a piece of paper — for different Brexit outcomes, although May is not legally-bound to follow their instructions. Also Read – Record number of 35 candidates in fray for SL Presidential pollsThe proposals put forward so include a customs union with the EU, remaining in the single market, holding a second referendum or stopping Brexit by revoking Article 50 — the formal notification for departure. The alternatives that will actually be voted on will be selected by speaker John Bercow on Wednesday and voting will take place at around 1900 GMT with the results expected at around 2100 GMT. Time has been set aside next Monday to try and whittle down the most popular options to a final plan. Parliament’s unprecedented power-grab was spearheaded by arch-EU MPs, who want to either reverse Brexit or preserve much closer economic ties with the remaining 27 states. Three members of May’s government quit in order to vote for the move, further piling pressure on their leader. However, she received a boost on Tuesday when influential Brexiteer Jacob Rees Mogg suggested he could back her deal in order to make sure the whole process was not stopped. Prominent Brexit supporter Boris Johnson has already indicated that he could back the deal, but only if May agrees to go, raising suggestions that she could announce plans for her departure at a meeting with Conservative MPs at 1700 GMT on Wednesday. “If the Prime Minister announces a timetable of departure, I think that’s going to swing a lot of people behind her deal, we could get it over the line,” said Conservative MP Nigel Evans. But the Democratic Unionist Party (DUP), the hardline Northern Irish power brokers who prop up the government, have poured cold water on the deal. The group’s Brexit spokesman Sammy Wilson said the party would rather see a one-year Brexit delay. “Even if we are forced into a one-year extension, we at least would have a say on the things which affect us during that time and would have the right to unilaterally decide to leave at the end of that one-year,” he wrote in the Daily Telegraph. “We won’t let the PM or the Remainer horde in parliament bully us into backing a toxic Brexit,” he said. Britain was originally due to exit from the EU on March 29, and MPs will vote on Wednesday to formalise the extension into law. It has already been written into international law and is expected to pass easily, with May’s office saying that “there would be uncertainty for citizens and businesses” if MPs were to reject it. A group of Brexit-supporting MPs however has said that holding the vote after the delay had already entered international law “created serious legal doubts about the legal situation surrounding the extension”.
Kolkata: Predicting that the BJP-led NDA would fall short of the majority mark of 272 seats in the ongoing Lok Sabha polls, Trinamool Congress has said regional parties will have a “big say” in the formation of next government but remained evasive on the issue of Prime Ministership. Trinamool Congress (TMC) leader Derek O’Brien, while expressing confidence that his party would have the third largest tally, also predicted that the NDA would break after the elections and “many” non-BJP parties would work together to form a government at the Centre. Prime Minister Narendra Modi is “trying to create an impression that he is ahead” which is nothing but a defensive tactic being projected as an “offensive” one, O’Brien, TMC’s Parliamentary Party leader in the Rajya Sabha, told IANS here. “The reality is that NDA is not even close to 272 (the majority mark). This is all actually defensive tactics but he (Modi) is trying to pretend that he is being on the offensive,” he said. TMC and the BJP are locked in a direct fight for the 42 Lok Sabha seats of West Bengal, with the saffron party giving a big push to its campaigning to ensure it bags a substantial number of seats here at the cost of ruling party of the state. The Prime Minister and BJP President Amit Shah have addressed several rallies in West Bengal over the last few weeks in a bid to raise the party’s poll prospects in the state where polling has already been held in 18 seats in four phases. Speaking about the likely poll-poll scenario, O’Brien insisted that the BJP will not be able to lead the NDA to form a government in New Delhi. “There are many parties which do not want to be (with them), especially the smaller and north east parties, which always stay with those forming the government,” the 58-year-old famous quizmaster-cum-author-cum-ad man said. “The NDA will break up after the results and maybe, all the north east parties will go,” he predicted and asked, “Why can’t these parties work with us?” In such a backdrop, all parties, which are not with the NDA, would work together, he added. “All I am telling you now is that the regional parties will have a big say (in forming an anti-BJP government),” he asserted. Asked whether the Congress would be part of the alternate coalition, the TMC leader said, “Our position is very clear. We work with all to defeat the BJP”. He went on to add, “The Congress and the CPI-M are working to defeat the Trinamool in Bengal. There is a Bengal match to be played and there is another match in Delhi and we understand there is difference between the two.” On whether his party would extend support to Rahul Gandhi for the Prime Ministership if the Congress does well, O’Brien said, “Such questions are to be answered after May 23… If the Congress gets 272 seats (in the 543-seat Lok Sabha), they will choose whoever they want as PM.” Asked to respond to Modi and Shah regularly ridiculing TMC chief Mamata Banerjee over her purported ambition to become the Prime Minister by contesting so few seats, O’Brien said, “We are100 per cent certain that we will continue to be the third largest party after the ongoing polls. We acknowledge two parties (BJP and Congress) may have bigger numbers than us.” Attacking the Prime Minister, he said, “I am not surprised at Modi’s remarks, as he does not believe in the Constitution of India that says 272 MPs will elect the leader. ” He went on to add, “He has to go. All of us are very clear that he will have to go.” Lambasting the Modi government, the TMC leader said it was destroying all institutions. “Parliament’s principal job is to legislate and scrutinise bills. 70 per cent of bills were scrutinised in India before the BJP came to power. But under Modi, only about 20 per cent of bills get scrutinized,” the Rajya Sabha member said. O’Brien did not agree that the contours of the Mahagathbandhan (grand alliance) envisaged at the January 19 Brigade Parade ground rally had failed to crystalise. “Everything is fine and Mahagatbandhan is absolutely in place. The BJP wants to pretend that it is not in place,” he said. O’Brien, who had worked for years as a creative head of an advertisement agency, quoted legendary advertisement guru David Ogilvy to punch a hole in the BJP campaign. “Ogilvy said if you have a good product, it may sell with bad advertising. The BJP sold a bad product with good advertising in 2014… They have sold all the dreams in 2014. Had they delivered even half of what they promised, they would have got three-fourth majority. But they have been an all-round failure,” he said.