Monday, January 30, 2006

Dry earwax? It's genetic

Genetics researchers have uncovered the key gene behind the mystery of human earwax.
Finally.
The report in Monday's Nature Genetics journal solves a long-running anthropologist's riddle - why many people in China and Korea, as well as elsewhere in Asia, have dry earwax while the rest of humanity enjoys the sticky variety.
The finding could represent the leading edge of some new reports about non-disease-related genes that are responsible for visible changes in human anatomy, population researchers say.
Geneticists had known the neighborhood of the earwax gene from previous work and decided to pin it down. The earwax riddle surprisingly comes down to a single gene, dubbed ABCC11, reports a Japanese team led by Koh-ichiro Yoshiura of the Nagasaki University Graduate School of Biomedical Sciences. The gene comes in two types, or alleles, corresponding to wet or dry earwax.
By examining 126 Japanese volunteers, the team determined that the dry-earwax gene is recessive, meaning both parents must pass a copy to their children for it to work. To chart a global earwax gene map, the team next looked at volunteers from 33 populations worldwide, from Native Americans to Ashkenazi Jews to Polynesian islanders. The dry-earwax allele probably arose "in northeast Asia and thereafter spread throughout the world," the team concludes.
"These results are amazing," says biological anthropologist Mark Shriver of the Pennsylvania State University in University Park by e-mail. Shriver says the Japanese team's success points the way to future finds of disease-related genes specific to certain populations worldwide, as well as glimpses of how evolution changes genes in people over time.
"We should recognize that we really know very little right now and embrace any chance to learn about how the forces of evolution have shaped human biology," he says.
In December, Shriver and colleagues, led by geneticist Keith Cheng of the Pennsylvania State University College of Medicine in Hershey, identified a gene responsible for much of the difference in human skin color between Europeans and Africans. Other genes probably govern skin hues elsewhere.
Taken with the earwax find, the trend is toward genetic research finding more of the non-disease genes responsible for physical differences in people worldwide, says anthropologist Joanna Mountain of Stanford University in Palo Alto.
"We're all curious what makes people different," she says.
Mountain suggests the dry-earwax allele probably originated within the past 30,000 years, "or even much more recently."
Intriguingly, the dry-earwax gene turns up fairly often in Native Americans, in about 30% of a sample of that population.
That suggests the emigrants from Asia who first populated North and South America brought the gene with them, the Japanese team says.
Dry earwax may have given people in northeast Asia some advantage during past periods of cold climate, not freezing as readily, the researchers suspect,
But "this is still pretty speculative," Mountain says.

幽默风趣的女人令男人却步

(中央社记者黄贞贞伦敦三十日讯)幽默风趣的男人令女人心动,但是谈笑风生的女性,却很难成为男性心仪的对象。最新研究发现,有幽默感的女人,容易让男人「相形见绌」,备感威胁,因此男人不会选择和这样的女性结为连理。 这份由西安大略大学University of WesternOntario、麻州大学University of Massachusetts等进行的研究,预定本周在「人类行为演化」期刊公布。英国「独立报」引述研究指出,男性在寻找人生伴侣时,对那些很会谈笑的女性,丝毫没有兴趣,但是如果只是「一夜情」或短暂的男女关係,有幽默感的女性仍会让男性心动进而追求。
负责这项研究的心理医师马汀Dr. Rod Martin分析指出,男性认为风趣幽默是男人的专利,加上有幽默感的女性,通常都是反应灵敏的聪明人,这让男性备感威胁,因此不敢「一亲芳泽」。 马汀和研究人员对数千名二十多岁的男女进行调查,询问男性「有幽默感的女人是不是很迷人时」,他们大多肯定表示「是」,但是再继续询问,他们是否愿意娶一个能让自己开怀大笑的女人时,答案几乎都是「不愿意」。 马汀说,男人在择偶时,宁可选择「知道如何欣赏幽默感」的女人,也不要「讲笑话让人开怀大笑」的女人。
(博讯2006年1月31日; boxun.com)

The nervous system mobilize hematopoietic stem cells

Study led by Mount Sinai School of Medicine may provide new hope for cancer patients and others with compromised immune systemsNew
study by Mount Sinai researchers may lead to improved stem cell therapies for patients with compromised immune systems due to intensive cancer therapy or autoimmune disease. The study is published in this week's issue of Cell.
A group, led by Paul Frenette, Associate Professor of Medicine at Mount Sinai School of Medicine, found that the sympathetic--or "fight or flight" branch--of the nervous system plays a critical role in coaxing bone marrow stem cells into the bloodstream. Bone marrow cells known as hematopoietic stem cells are the source for blood and immune cells.
Hematopoietic stem cell transplants are now routinely used to restore the immune systems of patients after intensive cancer therapy and for treatment of other disorders of the blood and immune system, according to the National Institutes of Health. While physicians once retrieved the stem cells directly from bone marrow, doctors now prefer to harvest donor cells that have been mobilized into circulating blood.
In normal individuals, the continuous trafficking of the stem cells between the bone marrow and blood fills empty or damaged niches and contributes to the maintenance of normal blood cell formation, according to the researchers. Although it has been known for many years that the mobilization of hematopoietic stem cells can be enhanced by multiple chemicals, the mechanisms that regulate this critical process are largely unknown, they said.
One factor in particular, known as hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF), is widely used clinically to elicit hematopoietic stem cell mobilization for life-saving bone marrow transplantation, said Dr. Frenette.
Several years ago, Dr. Frenette's group reported that a second compound, fucoidan, which is synthesized by certain seaweeds, could also spur the stem cells into action. The group speculated that the seaweed derivative might work by imitating a similar compound, called sulfatide, naturally present in mammalian tissues.
To test the idea, the researchers examined mice lacking the enzyme responsible for making sulfatide.
"Lo and behold, mice lacking the enzyme Cgt did not mobilize hematopoietic stem cells at all when treated with the stimulating factor G-CSF or fucoidan," Dr. Frenette said. "You don't get such dramatic results that often in science. We knew we had stumbled onto something important."
To their surprise, further study failed to connect the stalled stem cell movement to sulfatide. Rather, they found, the deficiency stemmed from a defect in the transmission of signals sent via the sympathetic nervous system. The products of Cgt contribute to the myelin sheath that coats and protects nerve cells, they explained.
Mice with other nervous system defects also exhibited a failure to mobilize bone marrow stem cells, they found. Moreover, drugs that stimulate the sympathetic nervous system restored stem cell movement into the blood stream in mice with an impaired ability to respond to norepinephrine, the signature chemical messenger of the sympathetic system.
"The nervous system plays an important role in producing signals that maintain the stem cell niche and retention in bone marrow," Dr. Frenette said.
"The new findings add another dimension of complexity to the processes involved in stem cell maintenance and mobilization and emphasize the interrelationships among the nervous, skeletal and hematopoietic systems," he added. "They all have to work together – to talk to each other – to produce blood and maintain stem cells."
The results suggest that differences in the sympathetic nervous systems of stem cell donors may explain "conspicuous variability" in the efficiency with which they mobilize hematopoietic cells into the bloodstream, the researchers said. Furthermore, drugs that alter the signals transmitted by the sympathetic nervous system to the stem cells in bone may offer a novel strategy to improve stem cell harvests for stem cell-based therapeutics, they added.
The unexpected findings by Frenette and his colleagues further "suggest that the pharmacological manipulation of the sympathetic nervous system may be a means of therapeutically targeting the stem cells in their niche for the purpose of either mobilization or, conversely, attracting stem cells to the niche following transplantation," they added. For more information.

Thursday, January 26, 2006

Master Genetic Switch Found For Chronic Pain

In experiments with mice, researchers have found that eliminating what appears to be a master genetic switch for the development of pain-sensing neurons knocks out the animals' response to "neuropathic pain." Such pain is abnormal pain that outlasts the injury and is associated with nerve and/or central nervous system changes. The animals rendered deficient in the gene, called Runx1, also showed lack of response to discomfort caused by heat and cold and inflammation. The researchers said that their findings, reported in the February 2, 2006, issue of Neuron, could have implications for the design of improved pain therapies. In their experiments, Qiufu Ma and colleagues studied the Runx1 gene because past research had shown it to code for a protein "transcription factor," which is a master regulator of multiple genes. Runx1 is one of a group of proteins that are key players involved in transmitting external sensory information, like pain and the perception of movement, to the spinal cord. In two other related papers in the same issue, Silvia Arber and colleagues and Tom Jessell and colleagues examine related aspects of the biological importance underlying the Runx transcription factors. For more information.

Friday, January 20, 2006

Gene Could Hold Key to Schizophrenia

Deleting a single gene in the brains of mice caused their memories to be affected in way that resembled schizophrenia in humans, U.S. scientists report. Before the gene was removed, the mice were trained to use external clues to look for chocolate treats buried in sand. But after being injected with a genetically engineered virus that deleted the NR1 gene, the mice were unable to learn a similar task. The study, by a team from UT Southwestern Medical Center in Dallas, appears in the current issue of The Journal of Neuroscience. For information.

Wednesday, January 18, 2006

Monogamy: dopamine ties the knot

Prairie voles form lasting pair bonds with their mating partners after a single experience of sexual activity, and this reward-related learning depends on dopamine. A new paper reports that two dopamine receptor subtypes contribute differently to the initial formation of pair bonds and to their maintenance by the promotion of selective aggression toward alternative mates.
Monogamy is rare among mammalian species, with only 3–5% forming lifelong pair bonds. The prairie vole Microtus ochrogaster forms such enduring bonds after a single initial mating encounter, but why are these prairie-dwelling critters 'addicted to love' when their mountain- and meadow-dwelling cousins indulge in lifelong promiscuity? The answer may lie in the same neurobiological culprit already implicated in drug addiction, the neurotransmitter dopamine. A group of scientists report a role for particular dopamine receptor subtypes both in establishing pair bonds in sexually naive male prairie voles and also in maintaining the integrity of the bond after it has formed. For more information, see Nature Neuroscience 9, 7 - 8 (2006).

Thursday, January 12, 2006

South Korean Team's Remaining Human Stem Cell Claim Demolished

In an announcement that researchers worldwide both expected and feared, Woo Suk Hwang's last remaining claim to have advanced the promising field of human embryonic stem (ES) cells has been declared fraudulent. In a report released on 10 January, a committee at Seoul National University (SNU) found that Hwang and his colleagues fabricated data in their breakthrough 2004 Science paper reporting the first creation of a stem cell line from a cloned human blastocyst. In an interim report in late December, the committee had already determined that a second paper by the team, published in 2005, was fraudulent (Science, 6 January, p. 22).
The final report concludes that Hwang and his colleagues did successfully clone a dog, which the scientists reported in Nature in August 2005. It also said that the Hwang team made some progress toward cloning early-stage human embryos. But the 2004 publication amounts to "none other than deceiving the scientific community and the public at large," the report says. (An English summary of the report is available on the SNU Web site at www.snu.ac.kr/engsnu.)
In the two papers published in Science, Hwang and his co-workers had claimed to have accomplished three firsts. The 2004 paper reported the cloning of a human blastocyst, through a process known as somatic cell nuclear transfer, and the derivation of ES cells from that cloned blastocyst; the 2005 paper reported the derivation of 11 human ES cell lines genetically matched to patients.
With both papers now thoroughly discredited, "we're back to the time prior to [Hwang's 2004] publication; there is no evidence at all that we can make [stem cells] from human embryos created through nuclear transfer," says Alan Trounson, a stem cell researcher at Monash University in Clayton, Australia. Hwang's team had also claimed phenomenal advances in efficiency in its 2005 paper, reporting that it needed fewer than 20 eggs to produce each stem cell line. Work in most other mammals suggests that it usually takes 100 to 200 eggs for one stem cell line, and many researchers say the unraveling of Hwang's work resurrects the question of whether the technique will ever be efficient enough for routine clinical application.
For more information: Science Magazine, 13 January 2006 , pp. 156 - 157.

Animal Eggs "To Grow Stem Cells"

Stem cell researchers are looking to use animal eggs as 'hosts' to grow human cells. A Chinese team has already claimed to have created human embryonic stem cells using rabbit eggs which had had their genetic material removed. UK experts said the option had to be considered because there were too few human eggs for research. Scientists say cells created using animal eggs would only be used in the lab, but critics condemned the plan. The recent controversy over South Korean researcher, Hwang Woo-suk, has added impetus to the need to find new sources of eggs, scientists say. For more information.

Friday, January 06, 2006

Brain Protein May Be Linked to Depression

Scientists have discovered a protein that seems to play a crucial role in developing depression, a finding that may lead to new treatments for the often debilitating illness — and fundamental understanding of why it strikes. Although problems with the mood-regulating brain chemical serotonin have long been linked to depression, scientists don't know what causes the disease that afflicts some 18 million Americans — or exactly what serotonin's role is. The newly found protein, named p11, appears to regulate how brain cells respond to serotonin, researchers from Rockefeller University and Sweden's Karolinska Institute report Friday in the journal Science. For more information.

Why hard work makes people happy

Researchers from Gothenburg University in Sweden have been studying published data on what makes people happy. They believe working to achieve a goal, rather than attaining it, makes people more satisfied - although they said good relationships were important.
UK experts agreed, but said the work had to match an individual's strengths. The Gothenburg team have been studying hundreds of interviews carried out with people across the world to find out what makes them feel fulfilled. They said winning the lottery or achieving a goal at work gave a temporary high, but it did not last. Instead, they found that working hard to reach a target was more fulfilling.
Lead researcher Dr Bengt Bruelde, from the university's philosophy department, said: "The important thing is to remain active. "From our research the people who were most active got the most joy. It may sound tempting to relax on a beach, but if you do it for too long it stops being satisfying." He said the full research would be published in the summer.
Averil Leimon, of the British Psychological Society, said: "Hard work is satisfying, but only if it suits you. "The work has to use a person's strengths otherwise it can be demoralising. " If it does, research has shown that the happiness is not even linked to the rewards that are on offer. But she added: "Relationships can also have a significant impact. Strong relationships whether through family, the church, friends or work can inoculate you against feeling low."

Tuesday, January 03, 2006

Timeline of A Controversy

A chronology of Woo Suk Hwang's stem-cell research
29 December 2005
The Seoul National University (SNU) team that has been investigating the South Korean researcher reports that there is no evidence that Woo Suk Hwang's stem cells came from patient-specific clones. Last week the investigators said that at least nine of eleven stem-cell lines in Hwang's 2005 Science paper were not what the paper claimed them to be (see 23 December entry below). Now they add that the remaining two lines also do not match the DNA of patients, as they were meant to. Instead they match cells from other, normal embryos created by in vitro fertilization. "Currently, we cannot find stem cells that have identical DNA fingerprint traces with patients and Hwang's team does not have scientific data to prove they did harvest patient-specific stem cells," says Jung-Hye Roe, director of research at SNU, in a press conference.
Science issues a statement saying: "There is no question in our minds that the stem-cell paper published 19 May 2005 by the journal Science needs to be retracted, and we are proceeding swiftly but appropriately in that direction." Science adds that they have not yet received official notification of the SNU investigation results, nor do they have all of the co-authors' signatures on a retraction agreement. They give the authors a deadline of 30 December, after which they say they will move towards an editorial retraction.
23 December 2005
A rapid investigation of Hwang's work at Seoul National University delivers a damning initial verdict: large amounts of the data in his 2005 landmark paper on patient-specific stem cells were fabricated. The university's investigating team announces in a televised press conference that the data in the 2005 Science paper came from just two cell lines, not 11 as claimed. This "cannot be some error from a simple mistake, but can only be seen as a deliberate fabrication", the panel says. Hwang says that these two stem cell lines, which are frozen in his lab, were derived from cloned embryos from specific patients. The university is doing tests to validate this. Investigation says Hwang lied Korean scandal will have global fallout.
16 December 2005
Science announces that Hwang and Schatten have written to request a retraction of their 2005 paper. Science editor Donald Kennedy says the journal received the letter hours before Hwang's press conference in South Korea (see entry below). Kennedy quoted from the letter during a press conference with reporters: "After analyzing the data, our team concludes the results...could not be trusted... Therefore we are requesting to withdraw the paper." Science says it must wait for the entire research team to consent to the retraction - a process that Kennedy says should take "days or weeks - not months."
Apology and defense - Hwang tells a press briefing that he and his team did create stem cells matched to individual patients, but that there were "mistakes made, human errors, in taking photographs and in the preservation of the stem cells''. Hwang says he will seek agreement from his co-authors to retract the Science paper, and will investigate how the mistakes were made. He adds that his team is thawing some frozen stem-cell lines from the study to authenticate them.
15 December 2005
Accusation of fake data: News stations across Korea report allegations from one of Hwang's collaborators that the work from May 2005 was based on fabricated data. Roh tells the MBC and two other television stations that Hwang had told him "there are no cloned embryonic stem cells".
13 December 2005
Schatten asks Hwang to retract their May 2005 Science paper. Schatten claims he has news of allegations from someone involved with the experiment that make him want his name removed from the paper. According to a release from the University of Pittsburgh, Schatten writes to Science and his co-authors: "My careful re-evaluations of published figures and tables, along with new problematic information, now casts substantial doubts about the paper's accuracy."
A letter from eight scientists, including Ian Wilmut, the cloner of Dolly the sheep, is published in Science calling for validation of Hwang's results: "We encourage Hwang's laboratory to cooperate with us to perform an independent test of his cell lines."
11 December 2005
Investigation opened - Seoul National University announces an investigation of Hwang's research, as requested by Hwang himself. The university hospital treats Hwang for stress and exhaustion.
05 December 2005
Investigation opened - University of Pittsburgh officials say they have opened a preliminary inquiry into the 2005 paper.
04 December 2005
Media outlets report that the MBC has apologized for the reporting tactics used in their 22 November programme on Hwang.
Mistake in the 2005 paper: According to Science editors, Hwang contacts them to alert them to erroneous duplications in some images published as part of the Supporting Online Material for the 2005 paper. "We made some unintentional error by using about 4 pictures redundantly," he says. Science determines that the redundant images did not appear in the PDF version of the accepted paper, but were inserted later, and says the mistake does not affect the paper's scientific conclusions.
01 December 2005
Accusation of mis-matched DNA - The MBC challenges the credibility of Hwang's data. Pursuing a tip-off, MBC gets five samples of patient-specific cell lines from Hwang and sends them, together with corresponding tissue samples, to an independent lab for DNA analysis. The programme reports that the DNA in one cell line does not match the tissue sample as it should. There are many possible explanations for MBC's findings, such as contamination. But the mismatch also raises the possibility that the embryonic stem-cell lines were not cloned from the stated patients. Hwang stands by his science.
According to Science, Moon Il Park, Director and Chair of the Institutional Review Board (IRB) on Human Subjects Research and Ethics Committees at Hanyang University Hospital, reveals to them the results of an investigation by the hospital IRB and Seoul National University IRB. It finds that: "1) two researchers under Dr. Woo Suk Hwang's supervision donated oocytes voluntarily without any coercion and 2) approximately US$1,445 was paid for direct expenses." This was not illegal or in violation of the Helsinki Guidelines of 1964, which prohibit coercion of research subjects. Park also told Science: "We strongly believe that the identified concerns have no impact on the validity of the scientific conclusions."
24 November 2005
Admission of payments for eggs: Hwang admits that his stem-cell research used eggs from paid donors and junior members of his team. He resigns from his official positions, saying he will continue his research.
22 November 2005
Seoul-based Munhwa Broadcasting Corporation (MBC) aired an investigative news programme showing further evidence that Hwang used eggs from junior members of his lab - the PD Diary program was called "The Myth of Hwang Woo-suk and Suspicions over Eggs."
21 November 2005
Sun Il Roh, a fertility expert at MizMedi Hospital in Seoul and a co-author of the landmark paper, admits that 20 eggs he procured and gave to Hwang for his 2004 study were paid for. Roh, a co-author on the 2005 paper, insists that Hwang did not know this.
12 November 2005
Schatten publicly cuts all ties to Hwang and his team at Seoul National University.
Mistake in the 2005 paper: The 2005 paper's authors provide Science with corrections to data in the paper's table 2, which are not thought to significantly alter the work's conclusions. The corrected table is published.
11 November 2005
According to Science, Schatten tells them he has stopped working with Hwang, because he believes Hwang misrepresented facts about consent issues related to the 2004 paper. Science asks Hwang to inform them of any concerns regarding his research. Hwang says he is looking into the matter.
10 November 2005
According to Science, Gerald Schatten, a biologist at the University of Pittsburgh and co-author of the May 2005 Science paper, alerts them to Korean press reports alleging that researcher Sun Il Roh has illegally traded ova. Schatten reassures Science that "none of the oocytes used in Professor Hwang's '04 or '05 Science papers were obtained from reimbursed women donors."
-- October 2005
Hwang resumes research, ending his voluntary suspension of activities.
19 October 2005
South Korea's government launches the World Stem Cell Hub, an international network for exchanging embryonic stem-cell lines and cloning technology. Hwang is to be its head.
03 August 2005
Cloned dogHwang and colleagues announce the first cloned dog - Snuppy, an Afghan hound (Lee B. C. et al. Nature436, 641; 2005). Some scientists hail his birth as a feat of ingenuity and perseverance, others question its value.
19 May 2005
Landmark paperHwang's team at the Seoul National University in South Korea reports it has established 11 embryonic stem-cell lines derived from the skin cells of individual patients (W. S. Hwang et al. Science 308, 1777-1783; 2005). The experiment is hailed as a huge step towards the medical use of person-specific cell lines. It also backs up the embryo-cloning claims in the team's February 2004 paper.
13 January 2005
The South Korean government approves Hwang's embryonic stem cell research. It is the first approval issued under the nation's new bioethics law.
01 January 2005
South Korean bioethics law comes into effect.
22 May 2004
The annual meeting of the Korean Bioethics Association calls on Hwang and a review board to answer questions about funding sources and the recruitment of egg donors. The association wants the National Human Rights Commission, an independent investigative body funded by the government, to pursue the case. But the commission's bioethics task force was not intended to investigate specific research projects.
-- May 2004
Ethical questions: Questions are raised about ethical practices in Hwang's work after investigations by Nature. It appears that some of the eggs may have come from junior members of the research team. This is potentially problematic because obtaining human eggs is painful and risky. Hwang denies any wrongdoing, but says that he will suspend his research until a new national bioethics law comes into effect in the new year.
-- February 2004
Biologists say that the South Korean breakthrough has alerted Western researchers to the pace of scientific and technological progress in East Asia. Hwang and colleagues attribute their success to a supportive cultural environment, well-funded laboratories, and legislation permitting human embryos to be cloned for research. Also critical to the researchers' success was their collection of 242 human eggs from 16 female volunteers.
12 February 2004
Landmark paper: Woo Suk Hwang from Seoul National University in South Korea and colleagues announced that they have cloned 30 human embryos and harvested stem cells from one of them (W. S. Hwang et al. Science 303, 1669-1674; 2004). The work makes headlines worldwide, as a step towards stem-cell therapies for diseases such as Parkinson's. Other groups have claimed to clone human embryos, but the supporting evidence has been sketchy. This success will also need further supporting evidence.

Gene Discovered Linking High-Fat Diet To Diabetes

A team at the University of California at San Diego has identified a gene that produces an enzyme that enables cells in the pancreas to recognize glucose and secrete insulin. Furthermore, a high fat diet suppresses the enzyme. In a study published in the research journal Cell, Dr. Jamey D. Marth and colleagues describe the gene that encodes GnT-4a, a glucose transporter enzyme. Without GnT-4a, beta cells in the pancreas fail to produce insulin when exposed to glucose and fat. Marth's team studied mice that did not carry the GnT-4a gene and found that the animals initially had high blood glucose levels, which progressed to beta cell failure followed by the development of type 2 diabetes. Normal mice that carried the GnT-4a enzyme but were fed a high-fat diet had reduced GnT-4a expression, followed by the chain of events leading to type 2 diabetes. "Our findings suggest that the current human epidemic in type 2 diabetes may be a result of GnT-4a enzyme deficiency," Marth commented in a university release. If further research confirms the findings, one possible clinical application would be the development of therapeutic agents that boost GnT-4a levels, and Marth is currently working on this. Agents that inhibit GnT-4a may also be useful in preventing a number of diseases inked to too much insulin production, such as cancer and cardiovascular disease. SOURCE: Cell, December 29, 2005. For more information.
Google