Research
Roundup
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Molecule
Could Yield Embryonic Stem Cells
Scientists
at Penn have identified a receptor that plays a key role in restricting
embryonic stem cells' pluripotency, their ability to develop into
virtually any of an adult animal's cell types. The work is the first
demonstration of a mechanism by which pluripotency is lost in mammalian
embryos, one that operates with nearly the precision of an on/off
switch in mouse embryos.
With
further study, the receptor, dubbed GCNF, could open the door to
new ways of creating embryonic stem cells without the ethical concerns
associated with sacrificing embryos. GCNF, short for germ cell nuclear
factor, was detailed in a recent paper in the journal Developmental
Cell.
"In
a sense, we're hoping that understanding what GCNF actually does
as it shuts down genes will let us turn back the clock on cellular
development," said senior author Hans R. Schöler, professor
of animal biology at the School of Veterinary Medicine. "This
knowledge may permit us to convert ordinary adult cells back to
embryonic stem cells for research purposes."
Dr.
Schöler, also the director of Penn's Center for Animal Transgenesis
and Germ Cell Research, said GCNF is the first factor known to repress
the key gene Oct4, which is expressed in pluripotent embryonic cells.
While GCNF is likely just one cog in a complex cellular machinery
that dictates pluripotency among the cells of mouse embryos, Dr.
Schöler's team believes it is a crucial player: without GCNF,
restriction of pluripotency does not occur properly and the embryo
eventually dies.
Active
in a very limited population of cells, Oct4 is the only gene known
to play an essential role in maintaining pluripotency. Whenever
its expression is suppressed, as by GCNF, pluripotency is lost.
Oct4's tightly regulated activity decreases steadily as embryonic
stem cells differentiate; GCNF eventually restricts Oct4's expression
in the body's somatic cells, leaving expression only in the germ
cell lineage.
With
President Bush's August declaration that federally funded research
would be limited to stem cell lines already harvested from frozen
embryos, many researchers are looking to alternative sources. Embryonic
stem cells' scientific appeal lies in their pluripotency: they have
not yet determined their ultimate role, so each has the potential
to become one of more than 200 tissue types in the body.
Dr.
Schöler was joined in the September Developmental Cell
paper by Guy Fuhrmann and Ian Sylvester of Penn; Arthur C.-K. Chung,
Kathy J. Jackson, Geoffrey Hummelke and Austen J. Cooney of Baylor
College of Medicine; Aria Baniahmad of the University of Giessen
in Germany; and Julien Sutter of the Centre du Neurochimie in Strasbourg,
France. Their work was funded by the NIH, the Marion Dilley and
David George Jones Funds and the Commonwealth and General Assembly
of Pennsylvania.
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Astronomers
Unveil Dark Matter Object in the Milky Way
Astronomers
from Penn, in collaboration with an international team of researchers,
have made the first direct detection and measurement of the properties
of a dark matter object in the Milky Way.
This
observation of a gravitational microlensing event--a temporary increase
in the brightness of a background star during the time it takes
dark matter to pass in front of it --is reported in the Dec. 6 issue
of Nature.
"By
measuring its mass, distance and velocity, we have established the
first complete picture of a massive compact halo object, or MACHO,"
said co-author Dr. Charles R. Alcock, professor of physics and astronomy
at Penn. "This demonstrates that microlensing light data, high-resolution
images and spectroscopy should allow astronomers to characterize
a significant fraction of the Milky Way's dark matter."
Dr.
Alcock, who serves as lead researcher on the international MACHO
Project, made much of his contribution to the work in his previous
capacity as director of the Institute of Geophysics and Planetary
Physics at the Lawrence Livermore National Laboratory in California.
The
team used the Hubble Space Telescope and the European Southern Observatory's
Very Large Telescope to take images and make spectra of a MACHO
microlens, making it possible to determine the mass of the MACHO
and its distance from the Earth. In this case, the MACHO is a star
600 light-years away with a mass 5 to 10 percent the mass of the
sun, making it a dwarf star and a faint member of the disk population
of stars in the Milky Way.
Previous
research has shown that if some of the dark matter were in the form
of MACHOs, its presence could be detected by the gravitational influence
MACHOs would have on light from distant stars. If a MACHO passes
in front of a star in a nearby galaxy, such as the Large Magellanic
Cloud, then the gravitational field of the MACHO will bend the light
and focus it into telescopes.
The
MACHO acts like a gravitational lens and causes the brightness of
the background star to increase for the short time it takes for
the MACHO to pass by. Depending on the mass of the MACHO and its
distance from the Earth, this period of brightening can last days,
weeks or months. Gravitational lensing can also be observed on much
larger scales around large mass concentrations, such as clusters
of galaxies. Since MACHOs are much smaller, they are referred to
as "microlenses."
The
form and duration of the brightening caused by the MACHO can be
predicted by theory and searched for as a clear signal of the presence
of MACHO dark matter. But in a normal event, the brightening alone
is not enough information to yield the distance to the MACHO, its
mass and velocity as independent quantities. It is only for unusual
events, such as this one, that more can be learned.
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Sachs Foundation
Promotes Entrepreneurship
The
Graduate School of Education and The Goldman Sachs Foundation are
preparing Penn students and K-12 educators to start new initiatives
in education. The Goldman Sachs Entrepreneurship in Education program
will nurture entrepreneurial-minded educators and support their
development of new initiatives.
"We
want to give educators access to training to become successful entrepreneurs,"
said Nancy Streim, GSE associate dean. "Educators need to be
at the forefront of reform efforts, thinking creatively about settings,
products and systems for educating America's children. Then they
need to get out there and do it."
A
central feature is the new "education track" of the Business
Plan Competition of the Wharton School. It provides mentoring, feedback
and cash incentives to Penn students with ideas for new businesses
in K-12 education. More than 20 teams of Penn students have drafted
education-related business plans, making them eligible to win as
much as $10,000 donated by The Goldman Sachs Foundation.
Other
components of the Goldman Sachs Entrepreneurship in Education program
include new courses that prepare Penn graduate students to start
their own education-related businesses and a summer institute in
entrepreneurship for K-12 teachers. In addition, a new executive-format,
doctoral-degree program in educational and organizational leadership
will offer and entrepreneurship concentration.
"The
Goldman Sachs Foundation's partnership with Penn illustrates our
commitment to excellence and innovation in education," said
Stephanie Bell-Rose, president of The Goldman Sachs Foundation.
"We look forward to a promising collaboration that will help
shape a new generation of social entrepreneurs."
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Key Risk
Factor for Canine Arthritis Identified
Drawing
upon an international database of some 16,000 dogs, researchers
at Penn have pinpointed what's believed to be the first solid predictor,
in any species, of future arthritis. The scientists have found that
laxity in the hip joint--several millimeters' worth of excessive
play between the ball of the femur and the hip's socket--correlates
strongly with the advent of hip arthritis later in a dog's life.
"The
relationship between hip laxity and arthritis in dogs is akin to
the relationship between high cholesterol and heart disease in humans,"
said lead author Dr. Gail K. Smith, professor of orthopedic surgery
and chair of the Philadelphia Department of Clinical Studies at
the School of Veterinary Medicine. "Hip laxity is no guarantee
of arthritis later in life, but it is a very solid risk factor."
The
finding, reported in the Dec. 15 issue of the Journal of the
American Veterinary Medical Association, could lead to new ways
of averting or minimizing the occurrence of canine arthritis, which
afflicts an estimated 70 to 80 percent of dogs in certain breeds.
Since a canine generation is just 30 to 36 months, Dr. Smith said
selective breeding to avoid high-laxity individuals could slash
the incidence of canine arthritis within 10 years.
Dr.
Smith, who began collecting data on arthritis in dogs in 1983, says
the physiological similarities between dogs and humans make it very
likely that joint laxity could similarly signal the likelihood of
arthritis in people, whose laxity could be remedied in humans with
medications. There is currently no such risk factor used to predict
the onset of arthritis among humans.
"Degenerative
joint disease is phenomenally prevalent in dogs," Dr. Smith
said. "This work will allow breeders and pet owners to make
informed decisions to help control and possibly eradicate the disease."
The
current study grew out of Dr. Smith's development of a now-licensed
system called the Penn Hip Improvement Program, or PennHIP. Some
1,400 veterinarians worldwide have been trained to use PennHIP to
measure hip laxity among dogs; it's from these clinicians that Dr.
Smith gathered data on the 15,742 dogs included in the JAVMA
paper.
Penn
remains the central repository for images collected using PennHIP,
allowing for population studies far beyond the fewer than 100 animals
involved in most veterinary studies. The number of dogs profiled
in the database is growing by roughly 3,000 a year.
Dr.
Smith's co-authors on the JAVMA paper include Philipp D.
Mayhew, Amy S. Kapatkin, Frances S. Shofer and Thomas P. Gregor,
all of the Philadelphia Department of Clinical Studies at the School
of Veterinary Medicine.
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Almanac, Vol. 48, No. 16, December 18, 2001
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