Human brain cells developed in lab, grow in mice

May 3, 2013 ? A key type of human brain cell developed in the laboratory grows seamlessly when transplanted into the brains of mice, UC San Francisco researchers have discovered, raising hope that these cells might one day be used to treat people with Parkinson's disease, epilepsy, and possibly even Alzheimer's disease, as well as and complications of spinal cord injury such as chronic pain and spasticity.

"We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way," said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF and co-lead author on the paper.

The researchers generated and transplanted a type of human nerve-cell progenitor called the medial ganglionic eminence (MGE) cell, in experiments described in the May 2 edition of Cell Stem Cell. Development of these human MGE cells within the mouse brain mimics what occurs in human development, they said.

Kriegstein sees MGE cells as a potential treatment to better control nerve circuits that become overactive in certain neurological disorders. Unlike other neural stem cells that can form many cell types -- and that may potentially be less controllable as a consequence -- most MGE cells are restricted to producing a type of cell called an interneuron. Interneurons integrate into the brain and provide controlled inhibition to balance the activity of nerve circuits.

To generate MGE cells in the lab, the researchers reliably directed the differentiation of human pluripotent stem cells -- either human embryonic stem cells or induced pluripotent stem cells derived from human skin. These two kinds of stem cells have virtually unlimited potential to become any human cell type. When transplanted into a strain of mice that does not reject human tissue, the human MGE-like cells survived within the rodent forebrain, integrated into the brain by forming connections with rodent nerve cells, and matured into specialized subtypes of interneurons.

These findings may serve as a model to study human diseases in which mature interneurons malfunction, according to Kriegstein. The researchers' methods may also be used to generate vast numbers of human MGE cells in quantities sufficient to launch potential future clinical trials, he said.

Kriegstein was a co-leader of the research, along with Arturo Alvarez-Buylla, PhD, UCSF professor of neurological surgery; John Rubenstein, MD, PhD, UCSF professor of psychiatry; and UCSF postdoctoral scholars Cory Nicholas, PhD, and Jiadong Chen, PhD.

Nicholas utilized key growth factors and other molecules to direct the derivation and maturation of the human MGE-like interneurons. He timed the delivery of these factors to shape their developmental path and confirmed their progression along this path. Chen used electrical measurements to carefully study the physiological and firing properties of the interneurons, as well as the formation of synapses between neurons.

Previously, UCSF researchers led by Allan Basbaum, PhD, chair of anatomy at UCSF, have used mouse MGE cell transplantation into the mouse spinal cord to reduce neuropathic pain, a surprising application outside the brain. Kriegstein, Nicholas and colleagues now are exploring the use of human MGE cells in mouse models of neuropathic pain and spasticity, Parkinson's disease and epilepsy.

"The hope is that we can deliver these cells to various places within the nervous system that have been overactive and that they will functionally integrate and provide regulated inhibition," Nicholas said.

The researchers also plan to develop MGE cells from induced pluripotent stem cells derived from skin cells of individuals with autism, epilepsy, schizophrenia and Alzheimer's disease, in order to investigate how the development and function of interneurons might become abnormal -- creating a lab-dish model of disease.

One mystery and challenge to both the clinical and pre-clinical study of human MGE cells is that they develop at a slower, human pace, reflecting an "intrinsic clock." In fast-developing mice, the human MGE-like cells still took seven to nine months to form interneuron subtypes that normally are present near birth.

"If we could accelerate the clock in human cells, then that would be very encouraging for various applications," Kriegstein said.

Other UCSF co-authors of the Cell Stem Cell study include Yunshuo Caroline Tang, a MD/PhD student; research specialists Nadine Chalmers and Christine Arnold; and UCSF postdoctoral fellows Daniel Vogt, PhD, and Ying-Jiun Chen, PhD.

Additional co-authors are Stanford University neurosurgery resident Derek Southwell, MD, PhD; Monash University professors of immunology and stem cell research Edouard Stanley, PhD, and Andrew Elefanty, PhD; and Yoshiki Sasai, PhD, from the RIKEN Center for Developmental Biology.

The research was funded by the California Institute of Regenerative Medicine, the National Institutes of Health, and the Osher Foundation. Arnold Kriegstein, Arturo Alvarez-Buylla, John Rubenstein, and Cory Nicholas are co-founders and shareholders of Neurona Therapeutics. An application for a patent, "In Vitro Production of Medial Ganglionic Eminence Precursor Cells," has been filed.

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The above story is reprinted from materials provided by University of California, San Francisco (UCSF), via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Cory?R. Nicholas, Jiadong Chen, Yunshuo Tang, Derek?G. Southwell, Nadine Chalmers, Daniel Vogt, Christine?M. Arnold, Ying-Jiun?J. Chen, Edouard?G. Stanley, Andrew?G. Elefanty, Yoshiki Sasai, Arturo Alvarez-Buylla, John?L.R. Rubenstein, Arnold?R. Kriegstein. Functional Maturation of hPSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development. Cell Stem Cell, 2013; 12 (5): 573 DOI: 10.1016/j.stem.2013.04.005

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/P711yUt8JeY/130503230313.htm

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DeansTalk - business management education: The Webby Awards ...

www.webbyawards.com

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TED Ed, winner of?Education

The University of Chicago (IT services), winner of School/University

Glassdoor, winner of?Employment

City Forward - IBM interactive, winner of Corporate Social Responsibility

TERRA: The Nature of Our World, winner of?Green

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MoMA Art Lab, winner of?Education Reference (Handheld)

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Source: http://www.deanstalk.net/deanstalk/2013/05/the-webby-awards-2013-education-schooluniversity-csr-employment-green-education-discoveryreference.html

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Death certificate: Boston bombing suspect died of gunshot wounds, blunt trauma to head, torso

BOSTON - A suspect in the Boston Marathon bombings died from gunshot wounds and blunt trauma to his head and torso, a funeral director said Friday.

Funeral home owner Peter Stefan has 26-year-old Tamerlan Tsarnaev's body and read details from his death certificate. The certificate cites Tsarnaev's "gunshot wounds of torso and extremities" and lists the time of his death as 1:35 a.m. on April 19, four days after the deadly bombing, Stefan said.

Tsarnaev died after a gunfight with authorities who had launched a massive manhunt for him and his brother, ethnic Chechens from Russia who came to the United States about a decade ago. Police have said he ran out of ammunition before his younger brother dragged his body under a vehicle while fleeing.

Tsarnaev's family on Friday was making arrangements for his funeral as investigators searched the woods near a college attended by 19-year-old Dzhokhar Tsarnaev, who was captured less than a day after his brother's death.

The funeral parlour is familiar with Muslim services and said it will handle arrangements for Tamerlan Tsarnaev, whose body was released by the state medical examiner Thursday.

The body initially was taken to another funeral home, where it was greeted by about 20 protesters.

Stefan, owner of Graham Putnam and Mahoney Funeral Parlors, said everybody deserves a dignified burial service no matter the circumstances of his or her death and he is prepared for protests.

"My problem here is trying to find a gravesite. A lot of people don't want to do it. They don't want to be involved with this," said Stefan, who said dozens of protesters gathered outside his funeral home, upset with his decision to handle the funeral. "I keep bringing up the point of Lee Harvey Oswald, Timothy McVeigh or Ted Bundy. Somebody had to do those, too."

Meanwhile, two U.S. officials said Dzhokhar Tsarnaev told interrogators that he and his brother initially considered setting off their bombs on July Fourth, American Independence day.

As part of the bombing investigation, federal, state and local authorities were searching the woods near the University of Massachusetts Dartmouth campus, where Dzhokhar Tsarnaev was a student. Christina DiIorio-Sterling, a spokeswoman for U.S. Attorney Carmen Ortiz, could not say what investigators were looking for but said residents should know there is no threat to public safety.

Dzhokhar Tsarnaev, who was found hiding in a tarp-covered boat in a suburban Boston backyard, faces a charge of using a weapon of mass destruction to kill. Three of his college classmates were arrested Wednesday and accused of helping after the bombing to remove a laptop and backpack from his dormitory room before the FBI searched it.

The April 15 bombing, using pressure cookers packed with explosives, nails, ball bearings and metal shards, killed three people and injured more than 260 others near the marathon's finish line.

The brothers decided to carry out the attack before Independence Day when they finished assembling the bombs, the surviving suspect told interrogators after he was arrested, according to two U.S. officials briefed on the investigation. The officials spoke on condition of anonymity because they were not authorized to discuss the ongoing investigation.

Investigators believe some of the explosives used in the attack were assembled in Tamerlan Tsarnaev's home, though there may have been some assembly elsewhere, one of the officials said. It does not appear that the brothers ever had big, definitive plans, the official said.

The brothers' mother insists the allegations against them are lies.

Meanwhile, the Department of Homeland Security ordered border agents to immediately begin verifying that every international student who arrives in the U.S. has a valid student visa, according to an internal memorandum obtained Friday by The Associated Press. The new procedure is the government's first security change directly related to the Boston bombings.

The order from a senior official at U.S. Customs and Border Protection, David J. Murphy, was circulated Thursday and came one day after President Barack Obama's administration acknowledged that one of the students accused of hiding evidence, Azamat Tazhayakov, of Kazakhstan, was allowed to return to the U.S. in January without a valid student visa.

Tazhayakov's lawyer has said he had nothing to do with the bombing and was shocked by it.

A benefit concert featuring Aerosmith, James Taylor and Jimmy Buffett is scheduled for May 30 at the TD Garden in Boston. The proceeds will go to The One Fund, which has taken in more than $28 million for those injured and the families of those who were killed.

The fund's administrator, Kenneth Feinberg, said Friday he plans to hold meetings with victims next week and begin cutting checks by the end of June.

___

Associated Press writers Bridget Murphy and Mark Pratt in Boston and Pete Yost, Eileen Sullivan and Alicia A. Caldwell in Washington contributed to this report.

Source: http://news.yahoo.com/death-certificate-boston-bombing-suspect-died-gunshot-wounds-235901215.html

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Computer simulations reveal the energy landscape of ion channels

Public release date: 3-May-2013
[ | E-mail | Share ]

Contact: Anna Stary-Weinzinger
anna.stary@univie.ac.at
43-142-775-5311
University of Vienna

This news release is available in German.

Every cell of our body is separated from its environment by a lipid bilayer. In order to maintain their biological function and to transduce signals, special proteins, so called ion channels, are embedded in the membrane. Anna Stary-Weinzinger and Tobias Linder from the University of Vienna and Bert de Groot from the Max Planck Institute of Biophysical Chemistry in Gttingen identified a key amino acid (phenylalanine 114), which plays an essential role for opening and closing of these ion channels. A conformational change of phenylalanine triggers opening of the channels.

"These proteins are highly selective, they can distinguish between different ions such as sodium, potassium or chloride and allow ion flux rates of up to 100 million ions per seconds", explains Stary-Weinzinger, leader of the research project and postdoc at the Department of Pharmacology and Toxicology of the University of Vienna. "These molecular switches regulate numerous essential body functions such as transduction of nerve signals, regulations of the heart rhythm or release of neurotransmitters. Slight changes in function, caused by replacement of single amino acids, can lead to severe diseases, such as arrhythmias, migraine, diabetes or cancer."

Knowledge of ion channel function provides the basis for better drugs

Ion channels are important drug targets. 10 percent of current pharmaceuticals target ion channels. A detailed understanding of these proteins is therefore essential to develop drugs with improved risk-benefit profiles. An important basis for drug development is a detailed knowledge of the functional mechanisms of these channels. However, there are still many open questions; especially the energy profile and pathway of opening and closure are far from being understood.

Computer simulations visualize ion channel movements

To watch these fascinating proteins at work, molecular dynamics simulations are necessary. Computational extensive calculations were performed with the help of the Vienna Scientific Cluster (VSC), the fastest high performance computer in Austria, a computer cluster operated by the University of Vienna, the Vienna University of Technology and the University of Natural Resources and Applied Life Sciences Vienna. With the help of VSC, the free energy landscape of ion channel gating could be investigated for the first time. The young researchers discovered that the open and closed channel states are separated by two energy barriers of different height.

Phenylalanine triggers conformational changes

Surprisingly, the dynamics of a specific amino acid, phenylalanine 114, are coupled to a first smaller energy barrier. "This side chain acts as molecular switch to release the channel from the closed state", explains Tobias Linder, PhD student from the University of Vienna. After these local changes, the channel undergoes large global rearrangements, leading to a fully open state. This second transition from an intermediate to a fully open pore is accompanied by a large second energy barrier.

###

This research project is financed by the FWF-doctoral program "Molecular Drug Targets" (MolTag), which is led by Steffen Hering, Head of the Department of Pharmacology and Toxicology of the Faculty of Life Sciences, University of Vienna.

Publication:

T. Linder, B.L. de Groot, A. Stary-Weinzinger: probing the energy landscape of activation gating of the bacterial potassium channel KcsA. PLOS Computational Biology, May 2013. DOI: 10.1371/journal.pcbi.1003058

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 3-May-2013
[ | E-mail | Share ]

Contact: Anna Stary-Weinzinger
anna.stary@univie.ac.at
43-142-775-5311
University of Vienna

This news release is available in German.

Every cell of our body is separated from its environment by a lipid bilayer. In order to maintain their biological function and to transduce signals, special proteins, so called ion channels, are embedded in the membrane. Anna Stary-Weinzinger and Tobias Linder from the University of Vienna and Bert de Groot from the Max Planck Institute of Biophysical Chemistry in Gttingen identified a key amino acid (phenylalanine 114), which plays an essential role for opening and closing of these ion channels. A conformational change of phenylalanine triggers opening of the channels.

"These proteins are highly selective, they can distinguish between different ions such as sodium, potassium or chloride and allow ion flux rates of up to 100 million ions per seconds", explains Stary-Weinzinger, leader of the research project and postdoc at the Department of Pharmacology and Toxicology of the University of Vienna. "These molecular switches regulate numerous essential body functions such as transduction of nerve signals, regulations of the heart rhythm or release of neurotransmitters. Slight changes in function, caused by replacement of single amino acids, can lead to severe diseases, such as arrhythmias, migraine, diabetes or cancer."

Knowledge of ion channel function provides the basis for better drugs

Ion channels are important drug targets. 10 percent of current pharmaceuticals target ion channels. A detailed understanding of these proteins is therefore essential to develop drugs with improved risk-benefit profiles. An important basis for drug development is a detailed knowledge of the functional mechanisms of these channels. However, there are still many open questions; especially the energy profile and pathway of opening and closure are far from being understood.

Computer simulations visualize ion channel movements

To watch these fascinating proteins at work, molecular dynamics simulations are necessary. Computational extensive calculations were performed with the help of the Vienna Scientific Cluster (VSC), the fastest high performance computer in Austria, a computer cluster operated by the University of Vienna, the Vienna University of Technology and the University of Natural Resources and Applied Life Sciences Vienna. With the help of VSC, the free energy landscape of ion channel gating could be investigated for the first time. The young researchers discovered that the open and closed channel states are separated by two energy barriers of different height.

Phenylalanine triggers conformational changes

Surprisingly, the dynamics of a specific amino acid, phenylalanine 114, are coupled to a first smaller energy barrier. "This side chain acts as molecular switch to release the channel from the closed state", explains Tobias Linder, PhD student from the University of Vienna. After these local changes, the channel undergoes large global rearrangements, leading to a fully open state. This second transition from an intermediate to a fully open pore is accompanied by a large second energy barrier.

###

This research project is financed by the FWF-doctoral program "Molecular Drug Targets" (MolTag), which is led by Steffen Hering, Head of the Department of Pharmacology and Toxicology of the Faculty of Life Sciences, University of Vienna.

Publication:

T. Linder, B.L. de Groot, A. Stary-Weinzinger: probing the energy landscape of activation gating of the bacterial potassium channel KcsA. PLOS Computational Biology, May 2013. DOI: 10.1371/journal.pcbi.1003058

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2013-05/uov-csr050313.php

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Moon: Tebow can't cut it in CFL

AP

The Bills added a considerable amount of speed to their WR corps during the draft.

The Dolphins are holding a job fair today for their stadium project which may not happen.

A vote for T.J. Moe as the Patriots? unheard of rookie free agent who could make an impact.

Jets QB Greg McElory is fired up about the team adding former Alabama teammate Dee Milliner.

Ravens seventh-round WR Aaron Mellette has to make a big jump in competition, but they like his size and potential.

All the pressure?s on Bengals QB Andy Dalton, with the extra weapons he was given this offseason.

Free agent tackle Winston Justice decided to not take his tour to the Browns after all.

Steelers sixth-round LB Vince Williams has an opportunity for playing time.

As you?d expect, the Texans are expecting first-round WR DeAndre Hopkins to contribute immediately.

A number of Colts players said a gay teammate would not be a problem in their locker room.

Gene Frenette of the Florida Times-Union says the Jaguars can?t afford to give WR Justin Blackmon many more chances.

The Titans released two other guys Wednesday, in addition to WR Lavelle Hawkins.

Improvements in the run game could be just what the Broncos needed.

The Raiders brought back LS Nick Guess.

If free agent LT Bryant McKinnie signs with the Chargers, he?ll be the oldest man on the roster.

The Cowboys think third-round S J.J. Wilcox has a chance to start.

Former Giants OT Roman Oben worries that an entire generation of former players is destined to struggle with life after football, but that current players have a better chance.

New Eagles DT Bennie Logan was one of eight LSU defenders drafted this year, and one of eight children in his family growing up.

The Redskins have invited a number of players to minicamp on a tryout basis, including Penn State QB Matt McGloin.

The Bears are still in the process of shuffling their (large) scouting department.

The Lions added three more undrafted rookies to their previous class of eight.

The Packers hope that drafting RB Eddie Lacy will keep them from having to trust luck to find a running game.

New Vikings DE Lawrence Jackson took the same minimum-wage deal the Lions offered, saying it was a ?good fit.?

The Falcons signed undrafted rookie K Casey Barth, the younger brother of Buccaneers K Connor Barth.

Former Panthers coach John Fox was back in his old home (where he still has a home), playing the pro-am at the local PGA Tour Stop.

The Saints are giving former LSU K Josh Jasper a tryout.

Bucs undrafted rookie CB Deveron Carr has the kind of bonus that indicates competition for his services.

The Cardinals signed some CBs in free agency, but trading for Javier Arenas proves you can?t have too many.

The Rams loaded up in the secondary with their undrafted rookie class.

The 49ers are willing to roll the dice, and even signed an undrafted rookie from a Division II school who didn?t play last year.

The Seahawks are getting praise for their offseason moves.

Source: http://profootballtalk.nbcsports.com/2013/05/02/warren-moon-says-the-cfl-is-no-place-for-tebow/related/

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Andy Dick on 'DWTS' exit: Carrie Ann's score hurt

TV

Michael Maloney TODAY contributor

13 hours ago

ABC

"Dancing With the Stars" has had its share of shocking saves on elimination nights over the years, but alas, funnyman Andy Dick benefit from one. After making valiant efforts for seven weeks, he and pro partner Sharna Burgess were sent home on Tuesday night?s results show.

"I think we were all hoping to be saved, but the odds were against us,? Burgess told TODAY in the post-show press line. ?Our scores were just too low."

Having earned only 17 points this week, the Dick's closest competitor on the scoreboard was soap star Ingo Rademacher, who had scored 22. That potentially surmountable gap widened when Rademacher and his pro partner, Kym Johnson, picked up an additional three points in a dance-off.

"The 5 we got from Carrie Ann (Inaba) on Monday really hurt us," Dick lamented to reporters after his ejection. "We?d never gotten one of those before."

Actually, Dick earned a 5 from head judge Len Goodman in the first week of the competition, but since then, his scores had improved -- until Monday night.

Related: 'Dancing's' Andy Dick sent home in emotionally charged episode

"She gave us that 5 compared to what other dancers were doing, not in comparison to our past dances," he said of Inaba's choice.

Dick singled out Inaba on-air for her low grade after he was told to leave. Does he harbor any hard feelings?

"I still love Carrie Ann," he said. "She responded to us the most (in the beginning). But then, in the end, she was the harshest."

The comic actor, who?s waiting for word on whether or not the sitcom pilot he shot for ABC last week will be picked up or not, said it?s going to be difficult giving up his dancing routine.

Related: 'Dancing' final four? The finale could see a shakeup

?Sharna and I are literally like a married couple,? Dick sighed. ?It?s going to be weird not seeing her every day.?

Dick and Burgess may not be learning any new dances together, but they are going to see each other. "We wanted one more week," he said. "But I?m still going to be here -- I?ll be sitting in the front row of next week?s show. Otherwise, it?d be like severing myself from my family. Now, I?ll be able to actually watch the dances."

Ironically, one of the dancers whom Dick will be watching next week is Burgess. She?s been tapped by Sean Lowe and Peta Murgatroyd to perform with them in the couple?s upcoming trio dance.

It won?t be the same, however, for Burgess.

"It?s been an amazing roller coaster," she said of her freshman stint as a pro dancer. "Andy and I bonded so much. I?m beyond proud of him. He?s overcome so many personal struggles. For me, it?s a greater honor to have been a part of that than winning a mirror ball trophy could be."

Source: http://www.today.com/entertainment/andy-dick-his-dancing-stars-ouster-carrie-anns-score-hurt-6C9693064

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Pharmacist accused of planting poisoned orange juice at Starbucks

By Bob Redell and Kris Sanchez, NBCBayArea.com

A 50-year-old pharmacist was arrested Monday night after police say she removed two bottles of orange juice from a bag - which they say were filled with rubbing alcohol - and placed them on the shelf with other refrigerated items at a Starbucks in San Jose, California.

San Jose Police Sgt. Jason Dwyer took Ramineh Behbehanian of San Jose into custody on an attempted murder charge because the orange juice contained what police said were lethal quantities of isopropyl alcohol. She is scheduled to appear in court Thursday.

She has no criminal record in Santa Clara County, according to court records. Late Tuesday, sources confirmed for NBC Bay Area that Behbehanian is a pharmacist working for a company owned by Johnson and Johnson.

Authorities are still not sure why she would have allegedly mixed rubbing alcohol with some orange juice in the afternoon, left the bottles in the refrigerated section alongside some yogurt and milk, and left the Snell Avenue store about 3:30 p.m. local time (6:30 p.m. ET).

"Why would she do such a thing?"?Chris Africa said, standing outside the Starbucks on Tuesday morning. "Was she trying to poison us?"

An alert customer standing behind her in line spotted her taking out her own bottles of juice from a green Starbucks bag, and put them in the refrigerator section. He also noticed a toxic smell. He told management. The woman might have felt under suspicion, police said, but a Starbucks employee got her license plate.

"A lot of people out there may have seen something and probably dismissed it," Dwyer said. "But I believe that person saved lives by doing that."

More news from NBCBayArea.com

The San Jose Fire Department responded to the scene, retrieved the bottles and tested the contents with hazardous materials equipment. It turned out, the bottles were filled with orange juice and rubbing alcohol.

On Tuesday morning, customer Brent Breyer said he was a little "apprehensive" about what happened at his usual Starbucks. He said he often brings his young daughter, who routinely grabs for items in the refrigerated section.

Police were able to track her down at her home, though no motive has surfaced.

A Starbucks spokesperson told NBC Bay Area that the company destroyed all the other juices in the Snell Avenue store out of an abundance of caution and had all other stores in Bay Area check their juice seals.?

All checked out OK.

Source: http://feeds.nbcnews.com/c/35002/f/653381/s/2b609833/l/0Lusnews0Bnbcnews0N0C0Inews0C20A130C0A50C0A10C179971390Epharmacist0Eaccused0Eof0Eplanting0Epoisoned0Eorange0Ejuice0Eat0Estarbucks0Dlite/story01.htm

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