Decisions, Decisions: Male Or Female? How Germ Cells Decide Whether To Be Sperm Or Eggs

The JAK/STAT Signaling Pathway - see here

Johns Hopkins biologists have determined how developing embryos tell their specialized "germ cells" whether to develop into a male's sperm or a female's eggs.
Present in both male and female embryos, germ cells are the precursors to both sperm and eggs. Unable to "decide" on their own which to become, however, germ cells must take "advice" from other cells within embryos as to which is the appropriate sex. The Johns Hopkins researchers have found that this advice is delivered by a sequence of chemical reactions called the "JAK/STAT" pathway. ("JAK/STAT" is an acronym for "Janus kinase/signal transducer and activator transcription.")
"Though we all know that the survival of the species depends on producing children, up until now we haven't understood how germ cells in the developing embryos decide whether to eventually become the sperm or eggs needed later for adult reproduction," said Mark Van Doren, assistant professor in the Department of Biology in the university's Krieger School of Arts and Sciences. "Now we know one way these other cells are talking to germ cells about sex."
Van Doren was co-author of the study, published in the July 28 issue of the journal Nature. The discovery promises to enhance understanding of infertility and even some forms of cancer and could eventually lead to the development of more effective treatments for both.
Led by Van Doren and post-doctoral fellow Matthew Wawersik, the Johns Hopkins team used specialized microscopes at the university's Integrated Imaging Center to look at certain molecules and cell types in fruit fly embryos. Though they already knew that the JAK/STAT pathway was an important means of various types of cell-to-cell communication, they discovered that embryos also were using that pathway to send germ cells signals regarding sexual identity.
"This work implicates that pathway as a key regulator of early decisions made by germ cells as to whether to eventually develop into eggs or sperm," Wawersik said.
Though the team's observations were limited to the pathway's role in fruit fly germ cell communication, Van Doren said the same conduit also is active in humans and mice. When communication via the JAK/STAT pathway misfires, diseases such as cancer can result, he said.
"Evolutionarily, germ cells are one of the most ancient cell types, needed by every type of animal to reproduce," Van Doren said. "Their developmental program is very similar, whether we are talking fruit flies or humans. As a result, these findings could eventually help us understand and treat defects in germ cell development that lead to human infertility and disease."

The team's work was supported by the National Institutes of Health and the Association of Regulatory and Clinical Scientists, as well as by an NIH National Research Service Award postdoctoral fellowship.

SOURCE: Johns Hopkins University

Using Computers And DNA To Count Bacteria, Measure Effects Of Metal Toxicity In Soil

Size and fundamental shapes of procaryotes revealed by three genera of Bacteria (l to r): Staphylococcus (spheres), Lactobacillus (rods), and Aquaspirillum (spirals).

LOS ALAMOS. Don't call them the Dirt Doctors, or Sultans of Soil, they're just clever Lab guys. A team from Los Alamos National Laboratory has a paper in this week's Science Magazine with a new way to count bugs in dirt. Bacteria, that is, in the highly complex world beneath our feet.

"Computational Improvements Reveal Great Bacterial Diversity and High Metal Toxicity in Soil," by Jason Gans, Murray Wolinsky and John Dunbar, of Los Alamos' Bioscience Division, describes a new approach to capturing the structure of bacterial communities in soil. In addition, the study provides insight into the devastating effects of metal pollution on those bacterial populations.
Why is this important, you ask? It turns out that in our technology-driven world, with biosensors in development for homeland security, emerging diseases surprising our medical communities and lifesaving medicines being extracted from jungle plants, we still don't know what's under our feet. The bacterial communities of every day soil are intensely complex, so diverse and densely populated, that normal measurement methods are overwhelmed.
"With improved analytical methods, we show that the abundance distribution and total diversity of soil-borne bacteria can be deciphered," said Dunbar.
"More than a million distinct genomes were present in the pristine soil, exceeding previous estimates by two orders of magnitude. When we examined the populations levels in metal-contaminated soil, we found the bacterial genetic diversity was reduced more than 99.9 percent," lead author Gans added.
The Los Alamos team used a technique known as DNA re-association, separating the two strands of all the bacterial DNA in a soil sample, blending them, and measuring the time it takes for the correct halves to properly reconnect.
As often happens at Los Alamos, where thousands of scientists from every imaginable discipline are gathered, the researchers form a multidisciplinary team, with Gans (biophysicist), Wolinsky (physicist) and Dunbar (microbiologist) using their varied backgrounds to solve these types of knotty questions. Their new approach enables far more accurate measures of the contribution of microbes to global biodiversity and more importantly the impact of human activities on the organisms responsible for sustaining all higher life forms.

SOURCE: Science Daily

Carbohydrate-based vaccine against cancer?

How can the immune system be made to attack tumor cells, which though degenerate are part of the body? The immune system must be presented with a component characteristic of tumor cells in the form of a vaccine, so that it can form antibodies against this antigen, as it is called.
If tumor cells then appear later, the antibodies recognize the antigen and bind to it, marking it as an enemy that must be destroyed. Among the differences between tumor cells and healthy cells is an abnormally high amount of certain oligosaccharides, which are involved in the formation of metastases. One of these saccharides would be a suitable antigen.

However, attempts to implement saccharides as the basis for a vaccine have thus far failed; unfortunately, carbohydrates are able to activate B-lymphocytes, but not T-lymphocytes. For successful immunization, the cooperation of both types of cells is needed. It is helpful to couple the sugar to a foreign carrier protein, but this is a poorly controllable reaction whose products can also trigger undesired immunological effects.

The research team headed by Geert-Jan Boons at the University of Georgia in Athens has found a clever alternative:
They have synthesized a three-component vaccine. Component one is Tn antigen, an oligosaccharide that is present in large numbers on the surface of certain human tumor cells. Tn is not present on healthy cells. Component two is the peptide YAF, which consists of a sequence of 20 amino acids found in a membrane protein of the meningitis pathogen Neisseria meningitides and activates T-Lymphocytes. The third component is the lipopeptide Pam3 Cys, a peptide with a fatty section modeled on a lipoprotein sequence found in E. coli bacteria. This should act as an additional "danger signal" for the immune system. Its fat content also make is easier to insert into liposomes, tiny balls of fat that act as "packaging" for the vaccine.

"Mice that have been immunized with this new vaccine
form antibodies against the Tn antigen," reports Boons. "We have proven that this saccharide, peptide, and lipid trio can, in principle, elicit animmune response - even against tumor antigens."

Author: Geert-Jan Boons,
University of Georgia, Athens (USA),
http://cell.ccrc.uga.edu/~gjboons/boons/Home.htm

Cancer treatment targets individual cells

Melbourne researchers have developed a cancer treatment which can identify
and kill individual cancer cells.

The treatment uses antibodies and DNA to target the cells, attached to a
radioactive atom, which destroys them.

The cancer-killing molecules have been effective in laboratory tests and
could undergo clinical trials within five years.

Dr Tom Karagiannis, of the Peter MacCallum Cancer Centre, says the treatment
is a first as it uses two levels of targeting.

"What we do is we target not only the cancer cell but also the DNA of the
cell, so it's the first time this has been done using these types of isotopes,"
he said.

Dr Karagiannis says the new treatment is the most specific yet developed.

"Our radiation is very, very specific at killing cancer cells," he said.

"It irradiates a volume of only one millionth of a millimetre and because it
does that, we can kill cancer cells specifically without doing damage to the
healthy tissue."

Source: ABC

Fluorescent protein basis for bluish coral

"Molecular and cellular biologists are familiar with the
popular green fluorescent protein, first isolated from a jellyfish, which is
used by researchers to label internal structures in living cells," said Jim
Remington, of the university's Institute of Molecular Biology.

"However,
it is less well known that the dramatic coloration of coral reef formations is
largely due to four closely related classes of proteins: cyan, green, yellow and
red fluorescent proteins. In addition, a fifth class of protein is not
fluorescent, but conveys a deep purple coloration to the tentacles of sea
anemones and similar animals."

The findings are published in the
Proceedings of the National Academy of Sciences.