Monster black hole found in tiny galaxy

Astronomers have for the first time found strong evidence for a giant black hole in a Lilliputian galaxy. The finding suggests that supermassive black holes could be twice as numerous in the nearby Universe as previously estimated, with many of them hidden at the centres of small, seemingly nondescript galaxies known as ultra-compact dwarfs.
Anil Seth of the University of Utah in Salt Lake City and his colleagues report the findings on 17 September in Nature. The team became intrigued by the ultra-compact dwarf galaxy M60-UCD1, some 16.6 million parsecs (54 million light years) from Earth, in part because its X-ray emissions suggested that it might house a black hole. Images taken with the Hubble Space Telescope showed that the galaxy harboured a high concentration of mass at its centre, but the team had no idea how heavy the putative black hole might be.
To weigh the beast, the researchers measured the velocity of stars whipping about the galaxy’s centre using an infrared spectrometer on the Gemini North telescope atop Mauna Kea in Hawaii. The high velocity of the stars is best explained by a central black hole that tips the scales at 21 million times the Sun’s mass, concluded Seth’s team. That is more than five times heavier than the black hole at the centre of the Milky Way — even though M60-UCD1 has an estimated diameter of about one-six-hundredth that of our home galaxy.
And whereas supermassive black holes typically have about 0.5% of the mass of the stars that are concentrated in the centre of their galaxies, the black hole in M60-UCD1 is about 18% of the mass of the galaxy's stars, enabling the gravitational monster to wield a much greater influence over the galaxy’s shape and structure. Recognizing the dominant role that some supermassive black holes have in the evolution of small galaxies is the most important result of the study, says astronomer Karl Gebhardt of the University of Texas at Austin.
“This is a very strong confirmation that small galaxies can have big black holes,” Gebhardt says. “This is a new class of galaxy — and that’s very exciting.”

Hiding in plain sight

At its current size, M60-UCD1 lacks the heft to have assembled such a massive black hole, but the galaxy might once have been much bigger, suggest Seth and his collaborators. They speculate that a collision with an even larger neighbouring galaxy, M60, stripped the outer parts of M60-UCD1 more than two billion years ago, leaving behind a dense remnant — the ultra-compact dwarf and its now oversized black hole.
The team has begun to examine several other relatively nearby ultra-compact dwarf galaxies that might also host supermassive black holes. Because these dwarfs are just as common as the large galaxies in which supermassive black holes are typically found, the number of giant black holes in the Universe today might be double what researchers have estimated, Seth says.
“We don’t yet understand how supermassive black holes form,” he notes. A better understanding of how they assemble could be gained by “getting a better census of the number of supermassive black holes, especially those in lower mass galaxies”.

Next-generation stem cells cleared for human trial

Japanese team will use 'iPS' cells  to treat patient with degenerative eye disease.
A Japanese patient with a debilitating eye disease is about to become the first person to be treated with induced pluripotent stem cells, which have generated enthusiastic expectations and earned their inventor a Nobel Prize. A health-ministry committee has vetted researchers' safety tests and cleared the team to begin the experimental procedure.
[Update 12 September: eye specialist Yasuo Kurimoto has now performed the procedure on the first patient, a 70-year-old woman..]


Masayo Takhashi, an ophthalmologist at the RIKEN Center for Developmental Biology (CDB) in Kobe, has been using induced pluripotent stem (iPS) cells to prepare a treatment for age-related macular degeneration. Unlike embryonic stem cells, iPS cells are produced from adult cells, so they can be genetically tailored to each recipient. They are capable of becoming any cell type in the body, and have the potential to treat a wide range of diseases. The CDB trial will be the first opportunity for the technology to prove its clinical value.
In age-related macular degeneration, extra blood vessels form in the eye, destabilizing a supportive base layer of the retina known as the retinal pigment epithelium. This results in the loss of the light-sensitive photoreceptors that are anchored in the epithelium, and often leads to blindness.
Takahashi took skin cells from people with the disease and converted them to iPS cells. She then coaxed these cells to become retinal pigment epithelium cells, and then to grow into thin sheets that can be transplanted to the damaged retina.
Takahashi and her collaborators have shown in monkey studies that iPS cells generated from the recipients' own cells do not provoke an immune reaction that causes them to be rejected. There have been concerns that iPS cells could cause tumours, but Takahashi's team has found that to be unlikely in mice and monkeys.
To counter further fears that the process of producing iPS cells could cause dangerous mutations, Takahashi's team performed additional tests of genetic stability. Guidelines covering the clinical use of stem cells require researchers to report safety testing on the cells before conducting transplants.
Takahashi appeared in front of a 19-member health-ministry committee for the safety of the clinical use of stem cells. She was flanked by Shinya Yamanaka, the biologist who first created iPS cells. Yamanaka shared the 2012 Nobl Prize in Physiology or Medicine for his breakthrough and now heads the Center for iPS Cell Research and Application in Kyoto. The health ministry declined Nature's request to comment on the kinds of genetic data that were presented, but said that no problems were found (see 'Stem cells cruise to clnic').
The team's iPS cells could now be surgically implanted into a trial participant within days, according to one RIKEN source; most of the Japanese media expect the procedure to take place some time this month. It will be performed by a surgeon at the Institute of Biomedical Research and Innovation, next to the CDB; RIKEN would not reveal the name of the surgeon. The team plans to monitor the cell recipient for one year after the operation. The pilot study will eventually involve six participants.
The news could be a welcome boost for the CDB, which since February has been mired in controversy over now-retracted papers concerning a procedure for generating stem cells (see the special collection 'The rise and fall f STAP'). The centre has been threatened with having its staff numbers cut in half.

When disease strikes from nowhere

When parents find that a child is not developing as expected, the protracted doctor visits, hospital stays and examinations only add to their distress — especially when no other family member has the condition and the standard tests on the child's blood and genes shed no light on the cause. The uncertainties, costs and anguish can be devastating to families, says Michael Friez, who directs the diagnostic laboratory at the Greenwood Genetic Center in South Carolina, a non-profit organization that analyses patients' genomes for clinicians.
Every clinical geneticist has experienced the inability to identify the cause of a child's neurodevelopmental disorder, adds Roger Stevenson, a clinical geneticist also at the centre. In the early 2000s, he began seeing a family with a toddler that had severe developmental problems, including a smaller-than-average head and intellectual disability.
It was more than a decade after their first visit before sequencing revealed that the boy had a mutation in a gene called DYRK1A, which is thought to have a role in brain development. The finding later helped to diagnose 16 other children in the United States and Europe who had the same symptoms — and although the condition has no cure, Stevenson saw that identifying the gene comforted the boy's parents, as did knowing that there were other children like their son.

New mutations

What was notable about this child's case was that it involved a de novo mutation — one that neither parent carries in their regular complement of DNA. De novo mutations can occur early in the development of the embryo. They can be in parents' gametes. Around 80% of de novo mutations seem to occur in the father's sperm and 20% in the mother's egg, says Joris Veltman, a geneticist at Radboud University Medical Center in Nijmegen, the Netherlands, who in July published a study of de novo mutations in people with intellectual disabilities¹.
Disorder-causing de novo mutations are hard to detect — they have to be identified among a host of other, innocuous genetic changes. A number of software-based approaches are emerging to sift through sequenced genomes in search of such mutations.
As sequencing instruments and databases of genetic information become increasingly available, tool-builders hope that their software contributions can become part of routine medical care. But sequencing and analysis are different from, say, a blood cholesterol test — samples have to be prepared for the instruments, which churn out the genome sequence in snippets that must be assembled and aligned to a reference genome, such as that curated by the Genome Reference Consortium.
The results are not perfect. A patient's genome sequence can contain errors — caused by the machine misreading a letter of DNA, for example — that must be filtered out computationally. And even then, a huge number of possibilities remains. DNA bases might differ from the reference, sequences can be inserted or deleted and the number of copies of a gene can vary. Of thousands of such changes, only one might have a role in a disorder.
The child's DNA is then compared with that of the parents. Again, not all differences between their genomes connect to the child's disorder. Researchers use software that includes statistical analyses to determine which changes are most likely to have a role. And the tools add information, such as published data about the links between genes and disease. These results help to create lists of genetic changes, or variants, ranked by likelihood of being linked to a disorder. But variant analysis is still an emerging science, and the software tools are still maturing. Despite this, in some cases the approach turns up a specific genetic change that is likely to be the cause of a disorder.
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