Stem cells: Integrating sight into the brain

Latest news from Nature 18 April 2012

This press release contains:

---Summaries of newsworthy papers:

Stem cells: Integrating sight into the brain

Neuroscience: Electrical signals are on the ball

Stem cells: Of mice and mended hearts

Cancer: New breast cancer subtypes

Comment: A space weather storm could catch us by surprise

Biology: The key to good bone health

Astrophysics: Mystery of cosmic ray origins continues

Geoscience: Filling in the gaps of environmental changes

Physics: Electrons doing the splits

Physics: Observation of the elusive coherent quantum slip phase

And finally… How listeners stay tuned

---Geographical listing of authors

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[1] Stem cells: Integrating sight into the brain (AOP)

DOI: 10.1038/nature10997

Evidence of functional rod-mediated vision following photoreceptor transplantation into adult mice that lack rod function is reported in Nature. The results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

Cell transplantation is a potential strategy for the treatment of blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells have been shown to migrate into the adult retina in mice and acquire the specialized features of mature photoreceptor cells, it is yet to be shown that the transplantation of these cells can actually improve vision.

To show that new rods can improve vision, Robin Ali and colleagues first optimized the rod transplantation procedure to increase the number of newly integrated photoreceptor cells in wild-type mice. They then tested the light-responsiveness of transplanted photoreceptor cells in a mouse model of congenital stationary night blindness. The transplanted cells formed synapses, and visual responses in the brain were enhanced, suggesting that visual information was being transmitted to the brain via the transplanted photoreceptors. Importantly, the mice who were recipients of the transplanted rods performed better on a task requiring low light vision.

The authors recognize that many further steps are required before these findings can be translated to the clinic but highlight that the work demonstrates that transplanted rod-photoreceptors can successfully integrate into retinal circuitry to improve vision.

CONTACT
Robin Ali (University College London, UK)

Tel: +44 20 7608 6817; E-mail: [email protected]

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[2] Neuroscience: Electrical signals are on the ball (AOP)
DOI: 10.1038/nature10987

A system based on decoding signals recorded from microelectrodes planted in the brain can restore voluntary control to paralysed muscles in two monkeys. The work, published in Nature, represents an advance towards similar restoration of hand function in human patients through brain-controlled functional electrical stimulation (FES).

Considerable efforts have been devoted to the development of FES systems in order to restore voluntary grasp function to patients who have suffered paralysis after a spinal cord injury. Current FES systems produce one or two grasps using pre-programmed information customized for each user and work because most actions only require a palmer or pinch grasp. However, normal hand movement is much more complex than this.

After training two monkeys to pick up and move weighted rubber balls using full muscle function, Lee Miller and colleagues simulated some of the effects of paralysis caused by spinal cord injury by injecting a local anaesthetic to block certain nerves at the elbow. They then used recordings from around 100 neurons in the motor cortex to predict the intended activity of the paralysed muscles when carrying out the same task. By stimulating up to five electrodes in the identified muscles they essentially bypass the monkey’s spinal cord, allowing for voluntary control of the paralysed muscles. The team report that the primates could then perform the task reliably despite complete paralysis of the flexor muscles in the forearm and hand. Without the FES they note that the monkeys were unable to grasp the ball despite exhibiting great neuronal discharge and electrical activity that correlated with previous attempts to do the task.

The authors predict that the monkey’s ability to execute unconstrained natural grasp is evidence that this FES neuroprosthesis could have an eventual clinical application. They caution, however, that their model of paralysis avoided many of the complications of actual spinal cord injury and was limited to the forearm and digit flexors. It is therefore important to recognize the possible coordination between remaining natural muscle control and this neuroprosthesis.

CONTACT

Lee Miller (Northwestern University, Chicago, IL, USA)

Tel: +1 312 503 8677; E-mail: [email protected]

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[3] Stem cells: Of mice and mended hearts (AOP)

DOI: 10.1038/nature11044

Reprogramming of cells in the hearts of mice into functioning cardiomyocytes ― cells that make the heart beat ― is demonstrated in Nature this week. Introducing a collection of reprogramming factors upon heart injury is shown to improve heart function and reduce the area of damaged tissue. The ability to regenerate adult heart tissue is a promising approach to treating heart disease, a major cause of death and disability worldwide.

Heart cells damaged during heart failure cannot function properly, and until recently it was thought that they could not be repaired. Using cultured cells, Deepak Srivastava and colleagues have previously shown that three transcription factors can induce conversion of cardiac fibroblasts, which make up half of mammalian heart cells, into cardiomyocytes. In the present work, they use the same approach to reprogram heart cells, and observe conversion of non-cardiomyocytes into cardiomyocytes in mice that have had heart attacks. Delivery of the transcription factors directly to the hearts of adult mice leads to attenuation of cardiac dysfunction following the heart attack and improvements in scar area.

CONTACT

Deepak Srivastava (University of California, San Francisco, CA, USA)
Tel: +1 415 734 2716; E-mail: [email protected]

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[4] Cancer: New breast cancer subtypes

DOI: 10.1038/nature10983

An analysis of nearly 2,000 breast cancer tumours reported in Nature this week identifies new subtypes with distinct clinical outcomes. The work provides a framework for understanding how genetic abnormalities may affect these outcomes.

Carlos Caldas, Samuel Aparicio and co-workers determine the drivers of different breast cancer subtypes by investigating the impact of inherited and acquired genetic changes on tumour characteristics. They define subtypes associated with specific clinical and molecular features in 997 breast tumours, which they validate in a second set of 995 tumours. Acquired genetic changes seem to influence nearly 40% of the genes expressed in tumours.

These data allow the authors to sub-classify breast cancers beyond the already established types, including both high-risk and favourable prognosis subtypes. Curtis and colleagues suggest that their findings may have implications for understanding therapeutic responses to targeted agents, and they advocate sequencing of the different subtypes.

CONTACT
Carlos Caldas (Cancer Research UK and University of Cambridge, UK)

Tel: +44 1223 404 193; E-mail: [email protected]

Samuel Aparicio (University of British Columbia, Vancouver, Canada)
Tel: +1 604 675 8207; E-mail: [email protected]

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Comment: A space weather storm could catch us by surprise (pp 311-313)

Although NASA and others are developing increasingly accurate forecasts to see geomagnetic space weather storms hours or days before they hit Earth, we still have no idea how big a storm we might encounter in future, says Mike Hapgood in a Comment piece in this week’s Nature. This leaves us unprepared, in the same way that Japan was unprepared for the size of the earthquake and tsunami that devastated the country last March.

We already know that a space weather storm the size of those that struck in 1859 or 1921 would prove disastrous, potentially leaving some areas without power for months and causing trillions of dollars of damage. But we should be preparing for a bigger storm, of the type likely to hit once in a thousand years. Sadly, we don’t know how big that storm might be, argues Hapgood.

To improve assessments of the hazard, Hapgood recommends digitizing old space weather data that is currently only in paper form, doing more statistical studies and developing more sophisticated process-based models. Systems that are at risk, including power grids and airlines, need such data to make informed decisions. Others, such as the financial industries that rely on signals from the Global Positioning System (GPS) to time-stamp monetary transactions, should be more open about their preparedness, he writes.

CONTACT

Mike Hapgood (Rutherford Appleton Laboratory, Chilton, UK)
Tel: +44 1235 446 520 or: +44 7899 908780; E-mail: [email protected]

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[5] Biology: The key to good bone health (AOP)

DOI: 10.1038/nature11000

A protein with a bone-protective effect described in Nature this week may represent a promising new therapeutic agent for bone and joint diseases. The protein, called semaphorin 3A (Sema3A), is expressed by cells that are responsible for bone formation. Mice treated with Sema3A show improvements in their bone health.

Normal bone mass is maintained by continuous breakdown (resorption) and formation of bone, but imbalances in these processes can lead to metabolic bone disorders, such as osteoporosis. As these processes are linked, treatments that can regulate the two synchronously are urgently needed. Hiroshi Takayanagi and colleagues identify Sema3A as a factor that both suppresses bone resorption and enhances bone formation. They demonstrate that administration of this protein in Sema3A-deficient mice, which have poor bone health, leads to an increase in bone formation.

The authors propose that Sema3A represents a long sought agent for achieving a favourable balance between bone resorption and formation. They conclude that these findings may pave the way for the development of therapeutic agents capable of encouraging bone regeneration.

CONTACT

Hiroshi Takayanagi (Tokyo Medical and Dental University, Japan)
Tel: +81 35 803 5471; E-mail: [email protected]

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[6] Astrophysics: Mystery of cosmic ray origins continues (pp 351-354)

Current theories of cosmic ray production in gamma-ray bursts may need to be revised, suggests a study in Nature this week. Very energetic astrophysical events are required to accelerate cosmic rays, such as gamma-ray bursts, which have been proposed as possible candidate sources. However, the latest findings rule out models in which gamma-ray bursts are the only sources of high-energy cosmic rays.

Nathan Whitehorn and colleagues used an array of detectors at the South Pole to search for neutrinos thought to be accelerated by processes associated with gamma-ray bursts. They find that the flux of energetic neutrinos predicted to be associated with gamma-ray bursts is at least 3.7 times lower than expected. This implies either that gamma-ray bursts are not responsible for the highest-energy galactic cosmic rays or that the efficiency of neutrino production is much lower than has been predicted.

The data presented here were obtained from the IceCube array and represent one of the first high-profile sets of results from the IceCube collaboration.

CONTACT

Nathan Whitehorn (University of Wisconsin, Madison, WI, USA)
Tel: +1 608 265 4978; E-mail: [email protected]

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[7] Geoscience: Filling in the gaps of environmental changes (pp 363-366)

A big gap in the rock record of past life and environmental conditions may represent an event that triggered the rapid expansion of marine animals around 550 million years ago. This proposal is based on an analysis of data from a prominent boundary between layers of rock known as the Great Unconformity and is published in this week’s Nature.

The Great Unconformity is a distinctive stratigraphic surface observed globally, most conspicuously in the Grand Canyon, where it separates 525-million-year-old sandstone from rocks dating back to around 740 million to 1,740 million years ago. Although Darwin and others have interpreted this ‘gap’ as a failure in the geologic record, Shanan Peters and Robert Gaines suggest that it marks a change in the marine environment. They propose that their data are indicative of enhanced continental weathering and rising oceanic alkalinity within expanding shallow seas. The resulting increase in available minerals may then have triggered the evolution of biomineralization (uptake of minerals for use in tissues) and the explosion of marine animals during the Cambrian era.

CONTACT

Shanan Peters (University of Wisconsin, Madison, WI, USA)
Tel: +1 608 262 5987 or: +1 608 320 9423; E-mail: [email protected]

Robert Gaines (Pomona College, Claremont, CA, USA)
Tel: +1 909 451 3073; E-mail: [email protected]

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[8] Physics: Electrons doing the splits (AOP; N&V)

DOI: 10.1038/nature10974

Previously researchers have observed spinons and holons in a one dimensional setup, and in this experiment the team observed a new, third type of excitation: the orbiton. However, they did not observe a single electron splitting into three independent entities, their results suggest that three entities are possible, but here they only saw two; the spinon and the orbiton, but the holon was suppressed.

Observations of a 'single' electron apparently splitting into two independent entities ― so-called quasi-particles ― are reported in this week’s Nature.

Electrons are a single subatomic particle defined by intrinsic properties of charge, angular momentum (spin) and an orbital degree of freedom. Whereas a free electron is indivisible, the behaviour of interacting groups of electrons in solids is subtly different; here they can each be considered as a bound state of three quasi-particles, each holding a separate quantum property. Even more counter-intuitive, if the dimensions of the solid are then reduced (for example, in a one-dimensional 'wire'), theory tells us that these quasi-particles can in principle be teased apart.

Electrons were first seen to behave as though they had split into two independent quasi-particles carrying either spin (spinons) or charge (holons) fifteen years ago. Justine Schlappa and colleagues describe a system where this fragmentation proceeds in a different way. They observe the orbital degree of freedom separating from that of the spin to yield a third distinct quasiparticle ― the orbiton.

CONTACT

Justine Schlappa (Helmholtz-Zentrum Berlin für Materialien und Energie, Germany)
Tel: +49 30 8062 13494; E-mail: [email protected]

Ralph Claessen (University of Würtzburg, Germany) N&V author
Tel: +49 931 31 85732; E-mail: [email protected]

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[9] Physics: Observation of the elusive coherent quantum slip phase (pp 355-358; N&V)

Detection of a fundamental phenomenon predicted by superconductivity theory is reported in this week’s Nature. This discovery may lead to new applications of superconducting electronics and advances in quantum measurement technology.

A century after the discovery of superconductivity, an effect predicted by the theory called the coherent quantum phase slip (CQPS) has remained undetected. CQPS is an analogue of the well-known Josephson effect; the latter concerns the coherent flow of electric charge between superconducting contacts, while the former is a coherent transfer of magnetic flux across a superconducting wire. Oleg Astafiev and co-workers report the direct observation of CQPS in a superconducting wire loop made from indium oxide. Just as the Josephson effect has found wide application (for example, in ultra-sensitive magnetic field detection), so the authors expect their demonstration of CQPSto open up new quantum techniques.

CONTACT
Oleg Astafiev (NEC Green Innovation Research Laboratories, Tsukuba, Japan)
Tel: +81 29 850 1188; E-mail: [email protected]

Alexey Bezryadin (University of Illinois at Urbana-Champaign, IL, USA) N&V author
Tel: +1 217 333 9580; E-mail: [email protected]

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[10] And finally… How listeners stay tuned (AOP)

DOI: 10.1038/nature11020

How are we able to tune in to a speaker of interest in a noisy, crowded environment? Insights into the way the auditory system achieves this feat, a puzzle known as the cocktail party problem, are reported in Nature this week. Understanding how the brain solves this problem may shed light on how these processes become impaired during ageing and in disorders of speech perception.

Humans have a remarkable ability to attend to a single speaker’s voice amid a background of complex speech, but the mechanisms through which the auditory system is able to extract intelligible speech under adverse listening conditions remain unclear. Nima Mesgarani and Edward Chang collected electrophysiological recordings from the cortex of two neurosurgery patients engaged in a listening task. The subjects listened to two simultaneous speech samples — different sentences spoken by different speakers — and were asked to indicate key details from one target speech sample. The authors found that population responses in non-primary auditory cortex reflected critical features of the attended speaker alone, even if the attended speech was received within a mixture of speakers. An algorithm trained with input from various speakers could predict which speaker the subject was attending to based on the patterns emerging in the secondary auditory cortex.

The findings show that the representation of speech in the cortex does not just reflect the external acoustic environment but also reveals perceptual aspects relevant to the listener’s intended goal. The research could further efforts to improve automatic speech recognition systems, which, at present, do not work well for more than one speaker.

CONTACT
Edward Chang (University of California, San Francisco, CA, USA)
Tel: +1 415 353 3489; E-mail: [email protected]

ALSO IN THIS ISSUE…

[11] Deformation cycles of subduction earthquakes in a viscoelastic Earth (pp 327-332)

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GEOGRAPHICAL LISTING OF AUTHORS:

The following list of places refers to the whereabouts of authors on the papers numbered in this release. For example, London: 4 - this means that on paper number four, there will be at least one author affiliated to an institute or company in London. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

AUSTRALIA
Adelaide: 6
Nedlands: 5

BARBADOS
Bridgetown: 6

BELGIUM
Brussels: 6
Gent: 6
Mons: 6

CANADA
Vancouver: 4
Sidney: 11
Victoria: 11
Winnipeg: 4

FINLAND
Jyväskylä: 9

FRANCE
Orsay: 8

GERMANY
Aachen: 6
Berlin: 6, 8
Bochum: 6
Bonn: 6
Dortmund: 6
Dresden: 8
Garching: 6
Heidelberg: 6
Mainz: 6
Stuttgart: 8
Wuppertal: 6
Zeuthen: 6

INDIA
Pune: 8

ISRAEL
Rehovot: 9

ITALY
Bari: 6

JAPAN
Chiba: 6
Osaka: 5
Sapporo: 5
Tokyo: 5
Tsukuba: 9

NETHERLANDS
Amsterdam: 8

NEW ZEALAND
Christchurch: 6

NORWAY
Oslo: 4

RUSSIA
Moscow: 9

SWEDEN
Stockholm: 6
Uppsala: 6

SWITZERLAND
Geneva: 6
Lausanne: 6, 8
Villigen: 8

UNITED KINGDOM
Cambridge: 4
Didcot: 8
Lancaster: 9
London: 1, 4
Nottingham: 4
Oxford: 6

UNITED STATES OF AMERICA
Alabama
Tuscaloosa: 6

Alaska
Anchorage: 6
Fairbanks: 11
California
Berkeley: 6
Claremont: 7
Irvine: 6
Los Angeles: 4
San Francisco: 3, 10
Delaware
Newark: 6
Georgia
Atlanta: 6
Illinois
Chicago: 2
Evanston: 2
Indiana
Indianapolis: 3
Kansas
Lawrence: 6
Louisiana
Baton Rouge: 6
Maryland
Baltimore: 1
College Park: 6
Greenbelt: 6
New Jersey
Piscataway: 9
New Mexico
Los Alamos: 6
New York
New York: 1
Stony Brook: 6
Ohio
Columbus: 6
Pennsylvania
Pittsburgh: 2
University Park: 6
South Dakota
Rapid City: 6
Wisconsin
Madison: 6, 7
River Falls: 6

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Tel: +44 20 7843 4502; E-mail: [email protected]

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Published: 18 Apr 2012

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