Genes Determining Asymmetry Probably Arose In The First Bilaterally Symmetric Organisms

Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.

The finding, reported online in advance of publication in Nature by University of California, Berkeley, researchers, indicates that the same genes have been responsible for establishing the left-right asymmetry of animals for 500-650 million years, originating in the last common ancestor of all animals with bilateral body organization, creatures that include everything from worms to humans.

"Previous studies indicated that the methods for breaking left-right symmetry in animals seem to differ widely, so there was nothing suggesting that the common ancestor of humans, snails and other bilateral organisms had a common strategy for left-right asymmetry," said Nipam H. Patel, UC Berkeley professor of integrative biology and of molecular and cell biology, and an investigator of the Howard Hughes Medical Institute.

"Indeed, scientists thought that one of the genes that is critical for setting up left-right asymmetry in vertebrates was only present in vertebrates and related groups and not in any other animals," said UC Berkeley post-doctoral fellow Cristina Grande. "But we found that gene in snails, which has a lot of evolutionary implications. This cellular pathway was present already in the ancestors of most animals."

The finding, the researchers say, could help to track down the ultimate cause of symmetry-breaking in snails and other organisms, and the cascade of gene activation that leads to complex shapes, such as coiled shells.

Despite humans' superficial symmetry - our left and right sides appear to be mirror images - we are anything but symmetric. Most people's hearts are towards the left side of the body, which means the left lung is slightly smaller to make room for the heart, and our intestines are arranged in an asymmetric coil. This asymmetry is unrelated to being left- or right-handed, a preference determined in the brain.

While a small percentage of people have their insides flipped, their overall internal arrangement is a mirror image of the norm. Anyone with a random arrangement of internal organs would be dead, Patel said, because his or her organs wouldn't fit together properly.

Other vertebrates are the same. In fact, scientists have identified a gene called "nodal" that - in all vertebrates checked to date - is expressed on the left side of the body and necessary to set up left-right asymmetry. If nodal doesn't work or is knocked out, internal organs are jumbled and the organism dies.

"In vertebrates, a set of genes tells the body it has to form a heart toward one side, and nodal is one of those genes," said Grande, who recently took a position at the Centro de Biología Molecular "Severo Ochoa" in Madrid, Spain.

"There are a lot of asymmetric molecules in the body, that is, molecules that are active on only one side of the body, but nodal is always expressed on the left side in all vertebrates, which is evidence of a conserved pathway," Patel said.

Genes similar to nodal have been found throughout the so-called deuterostomes, one of the three subgroups of bilateral animals that includes not only vertebrates, but also sea urchins and sea squirts.

But the most common lab animals, fruit flies and nematodes, apparently do not have a gene like nodal, despite their asymmetry. As a result, biologists have assumed that fruit flies and all other non-deuterostomes - snails included - use some other mechanism to establish right and left. Fruit flies and nematodes are in the clade Ecdysozoa, while snails and worms are members of the clade Lophotrochozoa.

Grande approached Patel four years ago to collaborate in a test of this assumption in snails, which have an obvious and easy-to-check handedness: Their shell either coils right, like a standard screw, or left. Patel, a biologist who focuses on the genetics and evolution of crustacean and insect development, such as the formation of segments and appendages in shrimps and crabs, invited Grande to join his lab, even though he had never before worked with snails.

Snail handedness becomes obvious very early in the embryo, Patel said. When the four-cell embryo divides to become eight cells, the new cells blossom from their predecessors in a clockwise spiral, in which case the snail ultimately forms a right-handed, or dextral, shell; or a counter-clockwise spiral, creating a left-handed, or sinistral, shell. Biologists had earlier shown that this decision is made by the mother snail, which dumps many proteins and RNA molecules into the egg to jump-start embryonic development and, in the process, imprints her offspring with specific characteristics.

"No one knows what that maternal gene is, and you can't track it down using the standard approach of looking for genetic markers because there are not yet enough markers in snails, so we looked for any molecular entry into the cause of asymmetry," Patel said.

That proved to be the genome of the marine limpet Lottia gigantea, a right-handed snail whose genome was sequenced recently by the Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, Calif. Grande looked for genes in Lottia similar to nodal, and found one, as well as a gene analogous to the gene, Pitx, which is activated by nodal and also involved in setting up left-right asymmetry in vertebrates.

She used this information to look for and find similar genes in the left-handed snail Biomphalaria glabrata, the fresh-water host of the parasite that causes schistosomiasis. Experimental tests showed that nodal and Pitx were active or expressed on the right side of embryos in the right-handed snail Lottia, and on the left side in the left-handed snail Biomphalaria.

A key test of the critical nature of nodal involved treating the snails with a chemical known to inhibit the activity of nodal. While most treated snails died, some lost the asymmetric expression of Pitx and, most strikingly, developed a straight shell, Patel said.

Grande has since found analogs of nodal in the genome of the marine worm Capitella, which was sequenced by JGI, suggesting that nodal is active throughout the Lophotrochozoa.

"Everybody thought using nodal and Pitx for left-right asymmetry was an invention of this one group, the deuterostomes," Grande said. "The fact that we find them setting up asymmetry in snails and worms means that is not true; the ancestor of all bilaterians already used these genes to set up left-right asymmetry."

Because the ancestral snail was right-handed and thus, presumably, expressed nodal and Pitx on the right side of the body - similar to sea urchins, an early offshoot of the deuterostome branch leading to humans - the authors propose that the common ancestor of all bilateral animals had left-right asymmetry controlled by nodal and Pitx expressed on the right side of the body.

The discovery also could help Grande and Patel track down the maternal factors that ultimately determine handedness in snails.

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Newly Identified Gene Powerful Predictor Of Colon Cancer Metastasis - Low Gene Activity - Higher Survival Rate

Cancer Researchers at the Max Delbruck Center for Molecular Medicine (MDC) Berlin-Buch and the Charite - Universitats Medizin Berlin (Germany) have identified a gene which enables them to predict for the first time with high probability if colon cancer is going to metastasize. Assistant Professor Dr. Ulrike Stein, Professor Peter M. Schlag, and Professor Walter Birchmeier were able to demonstrate that the gene MACC1 (Metastasis-Associated in Colon Cancer 1) not only promotes tumor growth but also the development of metastasis.When MACC1 gene activity is low, the life expectancy of patients with colon cancer is longer in comparison to patients with high MACC1 levels. (Nature Medicine, doi: 10.1038/nm.1889)*.

According to the National Institutes of Health in Bethesda, Maryland, USA, more than 108,000 people developed colon cancer in the US in 2008. Despite surgery, chemo- and radiotherapy, only 50 percent of patients can be cured because 20 percent of the patients have already developed metastasis by the time their colon cancer is diagnosed. In addition, one-third of patients whose treatment of the original colon cancer was successful will, nevertheless, go on to develop metastasis.

The MDC and Charité researchers are convinced that the identification of the MACC1 gene will aid medical doctors in identifying those patients as early as possible who are at high risk of developing life-threatening metastasis in the liver and the lungs. As a result, more intensive treatment and follow-up care could be offered to high risk patients.

MACC1 turns on a signaling pathway which is important for tumor growth and the formation of metastasis. Researchers call this pathway HGF/Met signaling pathway. Once MACC1 has activated this HGF/Met signaling pathway, tumor cells proliferate much faster, get rid of their ties within the cellular tissue, and eventually settle down as metastasis at various sights throughout the body far from the original tumor.

High MACC1 Levels - Higher Risk for Metastasis

The researchers discovered the MACC1 gene by comparing tissue from healthy persons with tissue from 103 patients with colon cancer between 20 to 88 years of age. Sixty (60) cancer patients had no metastasis at the time they underwent surgery.

Of these 60 patients, 37 had no metastasis five years after surgery and treatment. These patients were shown to have had low levels of MACC1 when first diagnosed with colon cancer. In contrast, 23 patients had developed metastasis in the course of five years after surgery. Researchers detected high levels of MACC1 in their colon cancer tissue. Thus, patients with high MACC1 levels have a much higher risk for developing metastasis than patients with a MACC1 gene that is not very active.

The researchers are convinced that MACC1 will enable physicians to decide if a patient needs a more intense therapy or if a less aggressive treatment is sufficient. "The expression analysis of MACC1 in the original tumor tissue will probably contribute to individualize and optimize colon cancer therapy", they assume.

Now the MDC and Charite researchers and their colleagues want to find out if the MACC1 gene also allows for a more precise prediction about the outcome of lung cancer, breast cancer, and stomach cancer.

MACC1, a newly identified key regulator of HGF-Met signaling, predicts colon cancer metastasis

Ulrike Stein1,2, Wolfgang Walther1,2, Franziska Alt1,2, Holger Schwabe2, Janice Smith1, Iduna Fichtner1, Walter Birchmeier1, Peter M. Schlag 1,2

1Max Delbrück Center for Molecular Medicine, Robert RössleStrasse 10, 13125 Berlin, Germany 2Department of Surgery and Surgical Oncology, Robert Rössle Cancer Hospital Charité University Medicine Berlin, Lindenberger Weg 80, 13125 Berlin, Germany

Foundation under Public Law
Directors:
Prof. Walter Birchmeier, PhD., Cornelia Lanz

Member of the Hermann von Helmholtz Association of National Research Centres

Further information: http://www.cancer.gov/cancertopics/types/colon-and-rectal

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Cellular Reprogramming: Science's Breakthrough Of The Year

In its annual list of the year's top ten scientific breakthroughs, the journal Science has given top honors to research that produced "made-to-order" cell lines by reprogramming cells from ill patients. These cell lines, and the techniques for producing them, offer long-sought tools for understanding -- and hopefully someday curing -- difficult-to-study diseases such as Parkinson's disease and type 1 diabetes.

Science and its publisher, AAAS, the nonprofit science society, now salute cellular reprogramming as the Breakthrough of the Year and recognize nine more of the year's most significant scientific accomplishments. The top ten list appears in a special feature in the journal's 19 December 2008 issue.

"When Science's writers and editors set out to pick this year's biggest advances, we looked for research that answers major questions about how the universe works and that paves the way for future discoveries. Our top choice, cellular reprogramming, opened a new field of biology almost overnight and holds out hope of life-saving medical advances," said deputy news editor Robert Coontz.

Two years ago, in experiments with mice, researchers showed that they could wipe out a cell's developmental "memory" by inserting just four genes. Once returned to its pristine, embryonic state, the cell could then be coaxed to become an altogether different type of cell.

This year, scientists built on this work with spectacular results. Two research teams took cells from patients suffering from a variety of diseases and reprogrammed them into stem cells. Many of these diseases are difficult or impossible to study with animal models, making the need for human cell lines to study even more acute.

The transformed cells grow and divide in the laboratory, unlike most adult cells, which don't survive in culture conditions. The cells could then be induced to assume new identities, including those cell types most affected by the diseases afflicting the patients who had donated the initial cells.

A third research team skipped the embryonic state altogether and, working with mouse cells, turned one type of mature pancreas cells, called exocrine cells, directly into another type, called beta cells.

The new cell lines will be major tools for understanding how diseases arise and develop, and they may also prove useful in screens for potential drugs. Eventually, if scientists can master cellular reprogramming so that it's more finely controlled, efficient and safe, patients may someday be treated with healthy versions of their own cells.

The other nine scientific achievements of 2008 follow. Except for the first runner-up, the direct detection of extrasolar planets, they are in no particular order.

Exoplanets - Seeing Is Believing: For the first time this year, astronomers directly observed planets orbiting other stars, using special telescope techniques to distinguish the planets' faint light from the stars' bright glare.

Expanding the Catalog of Cancer Genes: By sequencing genes from various cancer cells, including pancreatic cancer and glioblastoma, two of the deadliest cancers, researchers turned up dozens of mutations that remove the brakes on cell division and send the cell down the path to cancer.

New Mystery Materials: High-temperature superconductors are materials that carry electricity without resistance at inexplicably high temperatures. In 2008, researchers created a stir by discovering a whole second family of high-temperature superconductors, consisting of iron compounds instead of copper-and-oxygen-compounds.

Watching Proteins at Work: Biochemists encountered major surprises this year as they watched proteins bind to their targets, switch a cell's metabolic state and contribute to a tissue's properties.

Toward Renewable Energy on Demand: This year, researchers found a promising new tool for storing excess electricity generated from part-time sources like wind and solar power, on industrial scale. A cobalt-phosphorus catalyst that's relatively easy to come by can use electricity to split water to free its hydrogen, which can in turn be fed into fuel cells to produce electricity again.

The Video Embryo: In 2008, researchers observed in unprecedented detail the dance of cells in a developing embryo, recording and analyzing movies that trace the movements of the roughly 16,000 cells that make up the zebrafish embryo by the end of its first day of development.

"Good" Fat, Illuminated: In a study that may offer new approaches to treating obesity, scientists discovered that they could morph "good" brown fat, which burns "bad" white fat to generate heat for the body, into muscle and vice versa.

Calculating the Weight of the World: Physicists now have the calculations in hand to show that the standard model -- which describes most of the visible universe's particles and their interactions -- accurately predicts how much mass protons and neutrons have.

Faster, Cheaper Genome Sequencing: Researchers reported a flurry of genome sequences this year - from woolly mammoths to human cancer patients - aided by a variety of sequencing technologies that are much speedier and cheaper than the ones used to sequence the first human genome.

Areas to Watch: Science's predictions for hot science topics in 2009 include plants genomics, the elusive Higgs boson, speciation genes, ocean acidification, and neuroscience in court.

The special news features also looks at how the financial meltdown - the Breakdown of the Year - affected scientific research, and the major scientific collaborations getting off the ground in Europe.

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Congenital and conductive deafnes

I visited an old friend last Tuesday, I had a great time talking and catching up but that wasn't the one that i really can't forget, it was my friend's niece.

She was just around 2 years old. I called her but she didn't react or respond.

Then i found out that she was deaf.

My friend told me that it was Congenital deafness. And she is planning to send her to speech classes the moment the kid started schooling.

I was really concern because this is the first time i saw somebody that is deaf at a very young age.

So the moment i arrived i started my research about different type of deafness, and here's what i found.

Congenital deafness is one type of deafness that started from the moment you were born. It's like you already show hearing defects since you were young.

People don't usually react to different sounds that surround them.

You will know if a child has these kind of hearing defects if he's old enough to talk but still doesn't talk.

They should be wearing hearing aids and should undergo some speech training. Congenital deafness usually started from mothers who has German Measles.

Conductive deafness is a hearing loss that is cause by a defect of the external canal and the middle ear.

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Fate And Effects Of The Drug Tamiflu In The Environment

The research council FORMAS in Sweden has granted 574 000 euro to a new research project that will study the environmental fate and effects of the anti-viral drug Tamiflu on the development on influenza resistance.

Tamiflu is being stockpiled all over the world for use in fighting the next influenza pandemic. However, there are growing signs that influenza viruses may develop resistance to this vital pharmaceutical, because it is routinely prescribed for seasonal influenza.

- This research project is interdisciplinary and will combine studies on the environmental fate of the drug with in vivo studies of the development of Tamiflu resistant viruses say the project leader Björn Olsen at the Department of Medical Sciences Uppsala University.

This research project presents an innovative approach to studying the development of Tamiflu resistance in influenza viruses caused by environmental contamination which is a potential threat to one of our few defences against a future influenza pandemic.

Scientists from Uppsala University, Umeå University and Karolinska Institute will investigate the potential problem from an environmental chemical, virological and infectious diseases aspect.

A wide range of topics will be addressed; studies of the degradation of Tamiflu in sewage treatment plants will be combined with screening of the environmental levels in surface water in Japan. Japan is one of the world's top-per-capita consumers of Tamiflu and it has been estimated that approximately 40% of those that are infected by influenza viruses are treated with Tamiflu. This makes Japan one of the "Hot Spots" in the world and the research project has established collaboration with scientists at Kyoto University and several field sampling campaigns in Japan has been scheduled. Detected environmental levels will then be used in an in vivo Mallard infection model for detailed studies on the development of Tamiflu resistance in low pathogenic avian viruses. This will be combined with a screening study of the occurrence of resistant viruses in faecal samples from wild ducks in the vicinity of Japanese sewage treatment plants.

UPPSALA UNIVERSITET
P.O. Box 256
SE-751 05 Uppsala
http://www.uu.se

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Tamiflu In The Environment

The research council FORMAS, Sweden, has granted 5.9 million SEK to a new research project that will study the environmental fate and effects of the anti-viral drug Tamiflu on the development on influenza resistance.

Tamiflu is being stockpiled all over the world for use in fighting the next influenza pandemic. However, there are growing signs that influenza viruses may develop resistance to this vital pharmaceutical, because it is routinely prescribed for seasonal influenza.

This research project is interdisciplinary and will combine studies on the environmental fate of the drug with in vivo studies of the development of Tamiflu resistant viruses say the project leader Björn Olsen at the Department of Medical Sciences Uppsala University.

This research project presents an innovative approach to studying the development of Tamiflu resistance in influenza viruses caused by environmental contamination which is a potential threat to one of our few defences against a future influenza pandemic.

Scientists from Uppsala University, Umeå University and Karolinska Institute will investigate the potential problem from an environmental chemical, virological and infectious diseases aspect.

A wide range of topics will be addressed; studies of the degradation of Tamiflu in sewage treatment plants will be combined with screening of the environmental levels in surface water in Japan. Japan is one of the world's top-per-capita consumers of Tamiflu and it has been estimated that approximately 40% of those that are infected by influenza viruses are treated with Tamiflu. This makes Japan one of the "Hot Spots" in the world and the research project has established collaboration with scientists at Kyoto University and several field sampling campaigns in Japan has been scheduled. Detected environmental levels will then be used in an in vivo Mallard infection model for detailed studies on the development of Tamiflu resistance in low pathogenic avian viruses. This will be combined with a screening study of the occurrence of resistant viruses in faecal samples from wild ducks in the vicinity of Japanese sewage treatment plants.

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Abnormally short stature with normal body proportions

Growth hormone deficiency involves abnormally short stature with normal body proportions. It is a condition of inadequate production of growth hormone.Growth hormone deficiency can be categorized as either congenital (present at birth) or acquired.It is also known as Panhypopituitarism; Dwarfism; Pituitary dwarfism.

Causes:

Receiving brain radiation treatments for cancer,severe head injury,insufficient release of stimulatory hormone from the hypothalamus,insufficient production of growth hormone by the pituitary,decrease in IGF-1 hormones, lack of oxygen at birth,diseases in the pituitary gland, abnormalities in the hormone receptors, an autoimmune attack,mutations of specific genes,congenital malformations involving the pituitary,surgery in the area of the pituitary,auto immune inflammation (hypophysitis), severe head trauma, anatomical abnormalities,deficiencies of other hormones, including: Thyrotropins (control production of thyroid hormones) Vasopressin (controls water balance in the body) ,Gonadotropins (control production of male and female sex hormones) , adrenocorticotrophic hormone (controls the adrenal gland and its production of cortisol, DHEA, and other hormones) etc.


Symptoms:

Physical and psychological symptoms, including poor memory, social withdrawal, and even depression,loss of strength, stamina, and musculature,lowed or absent increase in height ,short stature,absent or delayed sexual development in an adolescent ,headaches ,excessive thirst with excessive urination ,reduced muscle mass and strength ,reduced bone mass and strength ,reduced physical, mental, and social energy and resilience , increased amount of fat around the waist, delayed tooth development, delayed onset of puberty , low energy , decreased strength and exercise tolerance,thin and dry skin.

Treatment:

Growth hormone deficiency is treated by growth hormone replacement. The goals of treatment are to increase growth in children and restore energy, metabolism, and body composition.Usually,somatropin (Humatrope, Genotropin, Norditropin, Nutropin, Saizen, TevTropin) is the growth hormone prescribed by doctors .Other Therapy-Radiation therapy to the pituitary gland. Synthetic growth hormone can be used for children with growth hormone deficiency.

Prevention:

Review child’s growth chart and add nutritional food in diet,


Alternative treatment:

Self-Care at home, patients should eat a balanced diet, get regular exercise, and get plenty of sleep.

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