20091218-10

Aligning the spins of carbon nuclei before injecting them into the body, makes MRI imaging that much easier.

MIT Technology Review  —  One of the major problems with magnetic resonance imaging machines is the huge magnetic fields required to make them work and the giant superconducting magnets that generate them. These magnets usually have a field strength of around 1.5 Tesla although some designs can reach 9 T or more. That makes them expensive. So expensive, in fact, that the cost of rest of the machine is chickenfeed in comparison.

So in recent years, various groups have looked at creating images with ultra low fields of just a few tens of microteslas.

Normally, the huge magnetic field is necessary to make protons in water molecules inside the body line up. Zapping these protons with radio waves knocks them out of kilter and as they realign themselves, the protons emit radio waves that can be used to construct an image.

Ultra low field MRI gets around the need for huge magnets by using a new generation of superconducting quantum interference devices or SQUIDS to pick up the signals used to reconstruct an image.

Now Vadim Zotev and buddies at the Los Alamos National Laboratories in New Mexico have another trick up their sleeve. One of the many astounding things that magnetic resonance imaging can do is track the changing presence of carbon-13 in the body. That’s important because it shows the body’s metabolism in action so researchers can see how diseases such as cancer and diabetes change the way it functions.

Here’s the trick. Instead of using a magnetic field to align the carbon-13 nuclei inside the body, they use a technique called dynamic nuclear polarisation to align the carbon nuclei before they are injected into the body.

That should make ultra low field MRI images of metabolism in action even easier to make and paves the way for real time videos of the metabolism at work using this kind of technique

Ref: arxiv.org/abs/0911.1137: Toward Microtesla MRI of Hyperpolarized Carbon-13 for Real-Time Metabolic Imaging

20091218-9

Rogue cell: An electron micrograph image shows a cancerous white blood cell from a patient with acute myeloid leukemia.  Credit: Andrejs Liepins / Photo Researchers 

 

Novel technique helps with bone marrow transplants for leukemia patients.

 

MIT Technology Review, December 17, 2009, by Michael Day  —  A transplant of healthy bone marrow stem cells may be the only hope for many patients with acute myeloid leukemia, a cancer affecting the production of healthy white blood cells. But after cancerous cells and a patient’s immune system have both been knocked out by radiation and chemotherapy, rebuilding that person’s immune capacity is a delicate, and potentially deadly, balancing act.

Mature donor immune cells provide short-term protection in the weeks after the operation. But these immune cells can also attack the host’s body, causing deadly graft-versus-host (GVH) disease. Now a novel way of preventing this reaction in bone marrow recipients, while protecting them from dangerous infections, has been developed by Italian and Israeli scientists.

The key is adding special immune-calming cells to the transplant material to prevent the donor immune cells from attacking the host, without compromising their ability to fight off dangerous infections. The researchers behind the work presented their findings this week at the Annual Meeting of the American Society of Hematology in New Orleans.

The problem of GVH disease is aggravated by the fact most transplants are provided by partially matched donors, because perfect matches–those with compatible proteins, called human leukocyte antigens–are usually unavailable.

When a patient and donor are not perfectly matched, high doses of stem cells, which mature into immune cells, can overcome rejection. The principle has been successfully pioneered in animal models by the coauthor of the new study, Yair Reisner of the Weizmann Institute of Science in Rehovot, Israel.

Following successful work in mice, Reisner joined forces with researchers at University of Perugia, Italy, to test the approach in more than 300 patients. The success rate for these partially matched transplants was found to be similar to that of transplants from matched donors picked from international bone marrow donor registries. To reduce the risk of GVH, mature immune T-cells have to be removed, meaning that post-transplant levels of life-threatening infection are high.

In the latest study, the Italian researchers infused 28 leukemia patients with a type of regulatory immune cell called CD4/CD25+ that had been selected from the donors’ own blood. These cells lessen T-cells’ tendency to attack host tissue, and have been shown to prevent GVH in animal studies. The “calming” immune cells have also been shown to keep other immune responses in check, including autoimmune attacks on the body’s own cells, but without hindering immune cells’ ability to fight infection.

The CD4/CD25+ cells were injected after the patients’ cancer cells and immune system had been knocked out by total-body radiation and chemotherapy. Next the patients were given transplants of bone marrow containing stem cells plus mature T-cells to help the depleted immune systems fight off viral and fungal infections in the short-term.

Of all the patients who received the entire treatment, only one developed GVH. In addition, the researchers claim that the reconstitution of the hosts’ immune systems appeared to occur more quickly than normal.

Study leader Massimo Martelli, head of hematology and clinical immunology at the University of Perugia, says the study shows that “T-regulatory cell-based therapy may be an innovative strategy to improve the outcome of patients who undergo bone marrow transplants.”

“We hope that this new method will reduce infection-related mortality and thus improve overall survival,” he adds.

Armand Keating, the director of hematology and a professor of medicine at the University of Toronto, says the new method is “an interesting and potentially important way of regulating T-cells” in stem cell transplants given to leukemia patients.

Keating adds that the method, if eventually validated, might prove particularly important for ethnic minorities who need marrow transplants. “The vast majority of donors on the registers are white people of northern European extraction. But with this method it might become possible to accept more partial matches from close family members such as siblings, or parents, if they are young enough,” he says. “With these kinds of transplants you need to move fast. Sometimes a day can make all the difference, so there isn’t time to find perfect matches on the register.”

However, Keating stresses that bigger, longer studies are needed. “With these patients, relapse is always a concern,” he says.

20091218-8

Stack of journals                                 Image: flicker/meviola

 

The-Scientist.com, December 17, 2009, by Victoria Stern  —  Which papers made the biggest splash this year? ScienceWatch, a website that tracks and analyzes trends in basic science research, compiles bimonthly lists of the 10 most cited papers. From those lists, The Scientist pulled the five papers in biology published in the last two years which were some of the most cited papers in 2009. The two topics that dominate the top five papers this year: genomics and stem cells.
(*All citation data, both ours and that of ScienceWatch, are from ISI.)  

5. A M. Wernig, et al.,In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state,” Nature 448: 318-24, 2007.

Citations this year: 237
Total citations to date: 512
Findings: Scientists successfully performed somatic-cell nuclear transfer (SCNT), producing stem cell lines and cloned animals for the first time using fertilized mouse eggs. This paper consistently ranked in the top 10 most cited papers in 2009, according to ScienceWatch.

4. E. Birney, et al., “Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, “Nature, 447: 799-816, 2007.
Citations this year: 267
Total citations to date: 618
Findings: The ENCODE project — ENCODE stands for the ENCyclopedia Of DNA Elements — set out to identify all functional elements in the human genome. After examining one percent of the genome, the paper revealed several new insights about how information encoded in the DNA comes to life in a cell.

3. A. Barski, et al., “High-resolution profiling of histone methylations in the human genome,” Cell, 129: 823-37, 2007.


Citations this year: 299

Total citations to date:: 560
Findings: This study looked at how histone modifications influence gene expression in more detail than previous attempts. Using a powerful sequencing tool called Solexa 1G, the researchers mapped more than 20 million DNA sequences associated with specific forms of histones, finding there were differences in methylation patterns between stem cells and differentiated T cells.

 

2. K.A. Frazer, et al., “A second generation human haplotype map of over 3.1 million SNPs,” Nature, 449: 854-61, 2007.
Citations this year: 389
Total citations to date: 588
Findings: Since the sequencing of the human genome in 2003, the International HapMap Project has explored single nucleotide polymorphisms (SNPs) — differences in a single letter of the DNA — to study how these small variations affect the development of diseases and the body’s response to pathogens and drugs. HapMap I, the original report, placed one SNP at roughly every 5,000 DNA letters. The newest map, featured in this paper, sequenced an additional 2 million SNPs, increasing the map’s resolution to one SNP per kilobase. The additional detail allows scientists to more closely investigate patterns in SNP differences, especially in hotspot regions, or concentrated stretches of DNA.

 

1. K. Takahashi, et al., “Induction of pluripotent stem cells from adult human fibroblasts by defined factors,” Cell, 131: 861-72, 2007.
Citations this year: 520
Total citations to date: 886
Findings: This work from Shinya Yamanaka’s lab in Japan was the first to demonstrate that induced pluripotent stem (iPS) cells can be generated from adult human dermal fibroblasts. Previous efforts by the team showed that iPS cells could be derived from mouse somatic cells. This paper was an easy top pick, receiving the most citations this year, according to ScienceWatch.

By Gabe Mirkin MD, December 18, 2009  —  A study on mice

may explain why it’s not so bad to get lots of infections when you

are young. 

 

Many studies show that children raised on farms are less likely

to develop allergies than those raised in cities.  If your immune cells

and proteins do not get a lot of practice and learn how to recognize

bacteria and viruses, they may attack pollen, mold, dust and other

particles that are not bacteria to cause allergies that show up as skin

rashes, nasal and lung obstruction and irritation.

 

 Researchers at The University of Marburg in Germany

worked with a line of mice that had been genetically programmed

to develop asthma.  They sprayed Acinetobacter lwoffii, a type

of bacteria found in farmyards. into the noses of pregnant mice,

and this prevented their newborns from developing asthma

(The Journal of Experimental Medicine, December 2009).

 

Asthma means intermittent obstruction of the bronchial

tubes that carry air to and from the lungs. It is caused by the

body’s immune cells and antibodies attacking something unknown

in the lungs to cause the bronchial tubes to fill with mucous,

the inner linings of the bronchial tubes to swell, and the muscles

surrounding the bronchial tubes to constrict and block the airways.

 

When a germ gets into your body, your immune cells and

antibodies recognize that the germ has surface proteins that are

different from your own surface proteins, and they attack it to try

to kill it. This causes swelling and irritation.  The Hygiene

Hypothesis is that exposure to lots of germs when you are young

gives your immunity practice in attacking germs so it will not

attack your own body tissues or non-germs such as mold, dust

or pollen.

 

This study shows that exposing a pregnant animal to

germs can prevent allergies in their offspring.  However, it is

unreasonable and probably dangerous to recommend exposing pregnant

women to infections.  We await further studies to see if extreme

cleanliness and protection from infections causes allergies.

 

 

***********************************************

 

Dear Dr. Mirkin:  Does coffee reduce risk for diabetes?

 

           Apparently yes.  Harvard researchers reviewed

18 studies of almost 500,000 people to find that drinking four

cups of coffee, decaffeinated coffee, or tea daily reduces the

incidence of Type 2 diabetes by up to 30 percent (Archives of

Internal Medicine, December 2009).  Each cup of coffee reduced

the incidence of diabetes by seven percent.

 

           Athletes have known for more than 60 years that taking

caffeine before a competition improves both speed and endurance

by increasing the amount of sugar that muscles use for energy.

Sugar requires less oxygen than fat to be converted to energy.

Caffeine may lower risk of diabetes by the same mechanism of

lowering blood sugar levels by driving sugar from the bloodstream

into muscles. Since decaffeinated coffee also helps prevent

diabetes, other components in coffee, such as lignans and

chlorogenic acids, may help prevent diabetes by their antioxidant

effects.

 

***********************************************

 

Dear Dr. Mirkin: My 80-year-old mother can barely walk; is it too

late for her to start an exercise program?

 

       No! A study from Israel shows that previously sedentary

people who start to exercise at age 85 are twice as likely to be

alive three years later as people of the same age who remained

sedentary (Archives of Internal Medicine, December 2009).  The

authors also found out that four hours a week of walking was as

beneficial as more vigorous or prolonged exercising.  They also

suffered less depression and loneliness and a greater ability to

perform daily tasks.

 

       Most of the two million years humans have been on earth,

they have been forced to be very active. Only recently have large

segments of the population exercised too little and eaten too much,

causing the “diseases of western civilization”: heart attacks,

strokes, diabetes and so forth.  You need to exercise almost every

day to protect your arteries from arteriosclerosis, the most common

cause of death in older Americans.  It’s never too late to start.

The winners of the American Society for Cell Biology’s annual image contest reveal the beauty within cells

20091218-4 

First Place Winner – “Save the Last Dance for Me”

The aptly named Celldance competition, an annual imaging competition sponsored by the American Society for Cell Biology (ASCB), recognizes still images and videos that are both scientifically important and visually engaging. “Most cell biologists are in large part motivated by the beauty they see in cells every day of their professional life,” Rex Chisolm, who chairs ASCB’s public information committee, said in a statement. “In one sense, working with cells is like working in an art gallery where the art changes every day.” The winning images, featured in this gallery, were announced last week at the society’s 49th annual meeting. The image above, entitled “Save the Last Dance for Me” took first place. This scanning electron image reveals the delicate hairs of the single cell organism Tetrahymena thermophila.  Photo Credit: Aswati Subramanian of Miami University in Oxford, Ohio

20091218-5

Second Place Winner – “Sea Creature Radiance.”

A multicolored micrograph of the diatom Arachnoidiscus. The diatom’s silicified cell wall forms a pillbox-like shell called a frustule, composed of overlapping halves that contain intricate and delicate markings.

Photo Credit: Michael Shribak of the Marine Biological Laboratory, Woods Hole, MA

20091218-6

Third Place Winner – “Protein Gymnasts”

This is the first image to reveal how the folding pathway of a protein is altered by a chaperone molecule.

Photo Credit: Graham Johnson of Scripps Research Institute in LaJolla, CA

20091218-7

Winner – Honorable Mention  —  “Cryptic Colonic Mountainscape.”

Using a riot of colors, this micrograph reveals colonic “crypts,” the intestinal stem cell niches that constantly replenish the epithelial cell population, in an adult mouse. Photo Credit: Kaelyn Male of Duke University Medical Center in Durham, NC

20091218-1

Graphic: Stephen Savage

 

Depletion of a Valuable Fish

20091218-2

Gulf Menhaden, Brevoortia patronus

The New York Times, December 17, 2009, by Paul Greenberg  —  If you are someone who catches and eats a lot of fish, as I am, you get adept at answering questions about which fish are safe, which are sustainable and which should be avoided altogether. But when this fish oil question arrived in my inbox recently, I was stumped. I knew that concerns about overfishing had prompted many consumers to choose supplements as a guilt-free way of getting their omega-3 fatty acids, which studies show lower triglycerides and the risk of heart attack. But I had never looked into the fish behind the oil and whether it was fit, morally or environmentally speaking, to be consumed.

The deal with fish oil, I found out, is that a considerable portion of it comes from a creature upon which the entire Atlantic coastal ecosystem relies, a big-headed, smelly, foot-long member of the herring family called menhaden, which a recent book identifies in its title as “The Most Important Fish in the Sea.”

The book’s author, H. Bruce Franklin, compares menhaden to the passenger pigeon and related to me recently how his research uncovered that populations were once so large that “the vanguard of the fish’s annual migration would reach Cape Cod while the rearguard was still in Maine.” Menhaden filter-feed nearly exclusively on algae, the most abundant forage in the world, and are prolifically good at converting that algae into omega-3 fatty acids and other important proteins and oils. They also form the basis of the Atlantic Coast’s marine food chain.

Nearly every fish a fish eater likes to eat eats menhaden. Bluefin tuna, striped bass, redfish and bluefish are just a few of the diners at the menhaden buffet. All of these fish are high in omega-3 fatty acids but are unable themselves to synthesize them. The omega-3s they have come from menhaden.

But menhaden are entering the final losing phases of a century-and-a-half fight for survival that began when humans started turning huge schools into fertilizer and lamp oil. Once petroleum-based oils replaced menhaden oil in lamps, trillions of menhaden were ground into feed for hogs, chickens and pets. Today, hundreds of billions of pounds of them are converted into lipstick, salmon feed, paint, “buttery spread,” salad dressing and, yes, some of those omega-3 supplements you have been forcing on your children. All of these products can be made with more environmentally benign substitutes, but menhaden are still used in great (though declining) numbers because they can be caught and processed cheaply.

For the last decade, one company, Omega Protein of Houston, has been catching 90 percent of the nation’s menhaden. The perniciousness of menhaden removals has been widely enough recognized that 13 of the 15 Atlantic states have banned Omega Protein’s boats from their waters. But the company’s toehold in North Carolina and Virginia (where it has its largest processing plant), and its continued right to fish in federal waters, means a half-billion menhaden are still taken from the ecosystem every year.

For fish guys like me, this egregious privatization of what is essentially a public resource is shocking. But even if you are not interested in fish, there is an important reason for concern about menhaden’s decline.

Quite simply, menhaden keep the water clean. The muddy brown color of the Long Island Sound and the growing dead zones in the Chesapeake Bay are the direct result of inadequate water filtration – a job that was once carried out by menhaden. An adult menhaden can rid four to six gallons of water of algae in a minute. Imagine then the water-cleaning capacity of the half-billion menhaden we “reduce” into oil every year.

So what is the seeker of omega-3 supplements to do? Bruce Franklin points out that there are 75 commercial products – including fish-oil pills made from fish discards – that don’t contribute directly to the depletion of a fishery. Flax oil also fits the bill and uses no fish at all.

But I’ve come to realize that, as with many issues surrounding fish, more powerful fulcrums than consumer choice need to be put in motion to fix things. President Obama and the Congressional leadership have repeatedly stressed their commitment to wresting the wealth of the nation from the hands of a few. A demonstration of this commitment would be to ban the fishing of menhaden in federal waters. The Virginia Legislature could enact a similar moratorium in the Chesapeake Bay (the largest menhaden nursery in the world).

The menhaden is a small fish that in its multitudes plays such a big role in our economy and environment that its fate shouldn’t be effectively controlled by a single company and its bottles of fish oil supplements. If our government is serious about standing up for the little guy, it should start by giving a little, but crucial, fish a fair deal.

Paul Greenberg is the author of the forthcoming “Four Fish: The Future of the Last Wild Food.”

20091218-3

External anatomy of the gulf menhaden (Brevoortia patronus). Fish illustration by Joseph Tomelleri (with permission), general annotation by A. Kane.