The second DNA string is also important

The FANTOM Consortium for Genome Exploration Research Group and Karolinska Institutet announce the publication of "Antisense Transcription in the Mammalian Genome" in Science, September 2nd 2005.


It has been known for over half a century that our genetic material occurs as a double strand of DNA molecules. Only one of these strands - the so-called sense strand - encodes for proteins, the building blocks of our cells that in turn make up our bodies. Then what about the other DNA strand - the antisense strand - can it also exert functions?

The answer is yes, it can produce so-called antisense genes that are read in our cells in the opposite direction of the real - sense - genes. This phenomenon has previously been regarded as rare, but scientists now show that it is actually the rule rather than the exception. More importantly, these antisense genes are now shown to be extensively used to modulate the expression of the conventional - sense - genes in our cells. Antisense genes are therefore likely to participate in the control of many, perhaps all, cell and body function.


These findings are also of interest because synthetic - man made - antisense molecules have been widely used to inhibit conventional genes, including applications as anti-viral and anti-cancer drugs, which are currently on the market or in clinical trials. It can now be argued that this same principle already has been used by nature on a massive scale.


Many of the described antisense genes are also unusual because they do not encode for proteins and therefore do not fit into the classical definition of a gene.

This concept of non-protein-coding RNA is supported by the data in an accompanying report entitled "The Transcriptional Landscape of the Mammalian Genome" by the FANTOM Consortium in the same issue of Science.

Since mammals, like humans and mice only have slightly more conventional genes (around 22,000) than a simple worm, the results clearly indicate that while proteins comprise the essential components of our cells, the development of multicellular organisms like mammals is controlled by vast amounts of regulatory noncoding RNAs that until recently were not suspected to exist or be relevant to our biology.

Moreover, since most proteins are similar among mammals it also suggests that many of the differences between species may be embedded in the differences in the RNA regulatory control systems, which are evolving much faster than the protein components.


If correct, these findings will radically alter our understanding of genetics and how information is stored in our genome, and how this information is transacted to control the incredibly complex process of mammalian development, with implications for the future of biological research, medicine and biotechnology.


Both of these publications are part of a long-standing international effort and represent an enormous body of work.


Prof. Claes Wahlestedt who is affiliated with Karolinska Institutet in Sweden as well as Scripps Florida and the RIKEN Genomic Sciences Center in Japan can be contacted for further information: Tel. +46-70-5848337, Email: claes.wahlestedtcgb.ki.se


Peer reviewed publication and references

"Antisense Transcription in the Mammalian Genome" by S. Katayama, Y. Tomaru, T. Kasukawa, K. Waki, M. Nakanishi, M. Nakamura, H. Nishida, C.C. Yap, M. Suzuki, P. Carninci, Y. Hayashizaki, C. Wells, M. Frith, T. Ravasi, K.C. Pang, J. Hallinan, J. Mattick, D.A. Hume, L. Lipovich, P.G. Engstrom, Y. Mizuno, M.A. Faghihi, A. Sandelin, A.M. Chalk, S. Mottagui-Tabar, Z. Liang, B. Lenhard and C. Wahlestedt in Science, September 2nd 2005.


Reference URL

info.ki.se/article_en.html?ID=4323


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Gene's Effects In Blood Vessels And High Blood Pressure In Older Adults

Scientists have identified the gene that sets off a sequence of events in the blood vessels of otherwise healthy adults that can lead to high blood pressure. The disease process eventually makes conditions in vessels ripe for the creation of blockages that can cause heart attacks, strokes and circulatory problems.



The finding in a study led by Ohio State University researchers might lead to new therapeutic options for high blood pressure, especially hypertension associated with aging. Obesity and aging contribute to increasing cases of high blood pressure, which currently affects an estimated 50 million Americans.



Despite more intensive treatments available for hypertension, little has been done to prevent it. A change in the structure of the blood vessels, called vascular remodeling, increases with age and triggers the onset of the disease. When remodeling occurs, blood vessel walls increase in thickness, decreasing the diameter of the channel through which blood normally flows.



The gene, called profilin 1, has been traced to a series of interactions within the smooth muscle cells of blood vessels that causes those cells to increase in size. This in turn narrows the channel through which blood flows, causing stress on vessel walls, injuring the lining of the vessel walls and making it easier for blockages to develop. By identifying this pathway, researchers hope to pinpoint the most effective therapeutic target to interfere with the disease process.



The researchers used genetically altered mice that produce excessive amounts of the human profilin 1 gene in the vascular smooth muscle cells and observed the changes to the vessels that followed, which led to high blood pressure by the time the mice were 6 months old - the rough equivalent to middle age in humans.



"We created the disease in the animals and then went backwards to understand how the disease developed. This is an important finding because vascular disease originates in the smooth muscle cells, which have significant impact on the dysregulation of blood pressure that leads to heart disease," said Hamdy Hassanain, assistant professor of anesthesiology at Ohio State University and senior author of the study. Hassanain also is an investigator in Ohio State's Davis Heart and Lung Research Institute.



The findings were published in the Dec. 28, 2007 issue of the Journal of Biological Chemistry.
















Blood vessels contain three important layers - the endothelium that lines the vessel walls, the smooth muscle cells responsible for regulating blood flow, and the lumen, the open channel through which blood travels. In healthy young humans, the production of compounds by the cells in these layers remains balanced, allowing for normal vessel function and unrestricted blood flow.



Hassanain developed a transgenic mouse that produces excess human profilin 1 in the smooth muscle cell area with the intent to cause stress in the vessel walls that leads to hypertrophy, or an enlargement of the smooth muscle cells that eventually leads to structural and functional changes in the entire vessel. The mice were developed to test the theory that the impaired regulation of the profilin 1 gene would eventually lead to high blood pressure, and observe how that happens.



"Vascular remodeling is a known problem as people get older. Their blood vessels tend to stiffen, even in healthy adults. This causes stress on the vessels, which leads to hypertension," Hassanain said.



At the heart of the vessel activities is a protein called actin within the smooth muscle cells, and its relationship to profilin 1. In the presence of too much profilin1, actin is transformed from a loosely configured protein into a more rigid fibrous state. This change in actin's nature increases the size and the stiffness of smooth muscle cells.



The cells undergo other changes that prepare them for cell division, but under these conditions, the vessel lining releases a substance, nitric oxide, that won't allow the cells to divide. The smooth muscle cells' resulting growth pushes inward, putting pressure on the lumen and restricting blood flow, resulting in high blood pressure.



"Profilin 1 is a tool that triggers events that make the vessel more constricted and leads to the signal that results in vascular remodeling. Because we have understood the pathway of the disease process, we might be able to control vascular remodeling," Hassanain said.



Once a vessel is remodeled, more trouble is typically ahead. Diseased vessels are often characterized by injuries to the endothelium, where the lining of the vessel loses its protective layer. Once the lining is injured and vulnerable, smooth muscle cells will start to migrate inward, creating sticking points for fats, debris and other blood remnants.



"That's the first hint of plaque. The smooth muscle cell migration is the tip of the iceberg of the plaque," Hassanain said. "We're talking about all vessels, but when we're talking about this narrowing effect in the brain, this could lead to stroke, and in the coronary artery, it could lead to heart attack. It's all the same phenomenon."







Other Ohio State co-authors of the study are Mazin Alhaj, Maqsood Chotani, Zeinb Aboelnaga, Mohamed Hassona, Gerard Nuovo and Jay Zweier, all of the Davis Heart and Lung Research Institute; Osama El-Sayed of cardiology; and Sheik Wisel of surgery; additional co-authors are Mariana Morris of Wright State University and Pascal Goldschmidt-Clermont of the University of Miami. First author Moustafa Moustafa-Bayoumi completed his Ph.D. in Hassanain's lab at Ohio State and is now at California State Polytechnic University .



Source: Hamdy Hassanain


Ohio State University

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It's Only Heartburn...or Is It? Chronic Heartburn A Risk Factor For Precursor To Esophageal Cancer

If you have or have
ever had chronic heartburn, you may be at risk for Barrett's esophagus, a
serious complication of chronic, severe gastroesophageal reflux disease
(GERD). Barrett's esophagus has been recognized as a major risk factor for
developing cancer of the esophagus, the seventh deadliest cancer in men in
the United States.



Barrett's esophagus is marked by cellular changes in the lining of the
esophagus, which can progress to low-grade, and then high-grade dysplasia
-- a level that is highly pre-malignant. These abnormal cellular changes
can lead to a type of cancer called esophageal adenocarcinoma, the fastest
rising malignancy in the United States, according to the National
Institutes of Health.



The Valley Hospital's Center for Barrett's Esophagus and GERD provides
cutting-edge diagnostic, treatment, management, and research services for
these related conditions. The Center is one of the most comprehensive on
the East Coast and unique to northern New Jersey. The physician team
includes board-certified gastroenterologists and thoracic surgeons.



Diagnostic and treatment methods available at the Center include
endoscopy, medications to reduce acid, minimally invasive surgical
procedures to repair hiatal hernias and to prevent acid reflux,
radiofrequency ablation to destroy abnormal cells, endoscopic mucosal
resection to remove nodules within Barrett's esophagus, and esophageal
cancer surgery.



Robert J. Korst, M.D., Medical Director of The Valley Hospital's Daniel
and Gloria Blumenthal Cancer Center, and Director of Thoracic Surgery, says
he and physicians at the Center for Barrett's Esophagus and GERD must take
a two-prong approach to treating Barrett's esophagus that both destroys the
abnormal lining and stops acid reflux.



"Radiofrequency ablation can get rid of the lining, but if the GERD is
not controlled, those abnormal cells can grow back and put the patient at
risk for cancer once again," he adds.




If Barrett's esophagus progresses into high-grade dysplasia or cancer,
the entire esophagus must be removed. Dr. Korst specializes in the
treatment and research of esophageal cancer and is highly experienced in
using both laparoscopic and traditional surgical methods to remove the
esophagus and construct a new one by stretching the stomach.



Barrett's esophagus is most prevalent in middle aged and elderly
Caucasian men but can affect anyone, even those who do not have obvious
symptoms of gastroesophageal reflux disease.


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Experimental Treatment For Type 1 Diabetes Patients Shows Promise

New research monitoring the effects of Islet cell transplantation resulted in near-normal metabolic control and decreased hypoglycemia. This research will be presented at the American Association of Clinical Endocrinologists (AACE) 17th Annual Meeting & Clinical Congress, on Friday, May 16th, at the Walt Disney World Dolphin Resort in Orlando.


During the 18 month study, physicians used Continuous Glucose Monitoring Systems to monitor the effects of the islet cell transplant procedure on patients with type 1 diabetes. The results were intriguing.


"Our findings suggest that the majority of patients with Type 1 diabetes who have received an islet transplant benefit from near normal metabolic control, with fewer and shorter episodes of hypoglycemia," said Lisa Gorn, DO, the study's primary author. "These patients also spent longer periods of time in normoglycemia overall.


At the 2008 AACE Annual Meeting diabetes will be taking center stage. A special symposium titled "Clinical Trials Targeting Glycemia: What Do We Expect to Learn?" will consider the impact of glucose control through studies including ACCORD, ADVANCE, VADT, and others. Related sessions of interest include "Insulin Resistance and Atherosclerosis: The Missing Link," and "Hypoglycemia: The Limiting Factor in the Glycemic Management of Diabetes."


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Non-Polyploid Colon Regions Are Linked To Colorectal Cancer - And More Common Than Previously Thought

Flat,
non-polyploid colorectal neoplasms (NP-CRNs) are difficult to detect,
but when examined, they appear to be common. Additionally they may have
a stronger association with colorectal cancer than polyps, which are
more routinely observed in examination, according to a study published
on March 5, 2008 in JAMA



Colorectal cancer, sometimes
simply called colon cancer, encompasses cancerous growths in the large
intestines and appendix. It is the second leading cause of cancer death
in the United States. Prevention strategies have focused on detecting
and removing polyploid neoplasms, which are abnormal growths resembling
polyps. More recently, however, it has been shown that colorectal
cancer can develop from NP-CRNs, which are flat or depressed
in
shape. These can be more difficult to detect, according to the authors
of the study: "Nonpolypoid colorectal
neoplasms are more difficult to detect by colonoscopy or computed
tomography colonography because the subtle findings can be difficult to
distinguish from those of normal mucosa [membrane]. As compared with
surrounding normal mucosa, NP-CRNs appear to be slightly elevated,
completely flat, or slightly depressed."



Since information is
limited regarding the true significance of NP-CRNs in colorectal cancer
development, Roy M. Soetikno, M.D.,
M.S., and colleagues with the Veterans Affairs Palo Alto Health Care
System, Palo Alto, California, investigated data from 1,819 patients
undergoing elective colonoscopy, in the hope of estimating the
frequency of NP-CRNs and to characterize the relationship of NP-CRNs to
colorectal cancer.



Patients were also classified into subgroups according to their
situations: the screening group, of asymptomatic
patients who had undergone average risk-screening colonoscopies; the surveillance
group, who had a personal or hereditary history of colorectal cancer;
or the symptomatic
group, who showed symptoms and indications associated with colorectal
neoplasms, including anemia, rectal bleeding, constipation, diarrhea,
positive results from a fecal occult blood test, weight loss, abdominal
pain, and inflammatory bowel disease.



In the whole group, NP-CRNs were present in 9.35% of patients.
According to subpopulation, the screening group showed 5.84%,
surveillance showed 5.84%, and symptomatic showed 6.01%. In cancers
that had not spread, or had spread in the tissue beneath the mucous
membrane the overall prevalence was 0.82%, while prevalence in the
screening population was 0.32%. It was also observed in the
surveillance and screening populations.



Overall, NP-CRNs were almost 10 times more likely to contain cancerous
tissue than polyploid lesions, regardless of size. The
depressed type of NP-CRNs showed the highest risk (33%.) NP-CRNs
containing cancer were generally smaller in diameter when compared with
polyploid cancerous regions.



"In conclusion, in
this population of patients at a single Veterans Affairs hospital,
NP-CRNs were a relatively common finding during colonoscopy. They were
more likely to contain carcinoma compared with polypoid neoplasms,
independent of lesion size. Recent studies have pointed out differences
in the genetic mechanisms underlying nonpolypoid and polypoid
colorectal neoplasms. Future studies on NP-CRNs should further evaluate
whether the diagnosis and removal of NP-CRNs has any effect on the
prevention and mortality of colorectal cancer and particularly focus on
their genetic and protein abnormalities," write the authors.



Editorial: Nonpolypoid Colorectal Neoplasia in the United
States



David Lieberman, M.D., of Oregon Health
& Science University, Portland VA Medical Center, Portland,
Ore.,
contributed an additional editorial in which he comments on the
findings of Soetikno and colleagues. "[Nonpolypoid
colorectal neoplasms] may be biologically distinct from polypoid
lesions and appear to be more likely to harbor malignant features.
Detection and complete removal at colonoscopy may be challenging. The
current study emphasizes the importance of quality in the performance
of colonoscopy," he writes. "The optimal methods for enhancing
colonoscopic imaging of NP-CRNs are uncertain. ??¦ Additional studies are
needed to determine whether imaging modalities such as computed
tomography colonography will be able to detect NP-CRNs. Finally,
longitudinal studies are needed to determine whether patients with
NP-CRNs require more intensive colonoscopic surveillance compared with
patients with polypoid lesions of similar size and histology."



Prevalence of Nonpolypoid (Flat and Depressed) Colorectal Neoplasms in
Asymptomatic and Symptomatic Adults

Roy M. Soetikno; Tonya Kaltenbach; Robert V. Rouse; Walter Park;
Anamika Maheshwari; Tohru Sato; Suzanne Matsui; Shai Friedland

JAMA. 2008; 299(9):1027-1035.

Click
Here For Abstract



Nonpolypoid Colorectal Neoplasia in the United States: The
Parachute Is Open

David Lieberman

JAMA. 2008; 299(9):1068-1069.

Click
Here For Extract



Anna Sophia McKenney

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MIT's MicroRNA 'Sponges' Could Aid Cancer Studies

MIT researchers have developed a new way to study the
function of microRNA, tiny strands of genetic material that help
regulate at least 25 percent of a cell's genes.



The new technique could shed light on microRNA's hypothesized role in
tumor development. Malfunctions in microRNA have been linked with
cancer, but very few direct relationships have been established
between specific microRNAs and the genes they regulate.



That could change, however, now that MIT Institute Professor Phillip
Sharp and his colleagues have found a way to inhibit the activity of
microRNA by genetically altering cells.



The technique, described in the August 12 online issue of Nature
Methods, could "provide a tool to identify specific genes that are
being regulated by microRNAs," said Sharp.



MicroRNA consists of short strings of about 22 nucleotides, the
building blocks that make up RNA and DNA. MicroRNA binds to messenger
RNA (mRNA), preventing it from delivering protein assembly
instructions, thereby inhibiting gene expression.



Sharp, who is affiliated with MIT's Biology Department and Center for
Cancer Research, said microRNA exists in every cell and controls a
wide range of cell regulatory activities.



The MIT team has found a way to block microRNA activity by tricking
cells into producing a microRNA "sponge," which soaks up microRNA and
renders it ineffective. By de-activating microRNA, researchers can
observe the resulting effects and determine which genes the microRNA
is targeting.



The new technique could shed more light on microRNA's role in tumor
development: Earlier studies have shown that a type of microRNA known
as let-7 inhibits a cancer-inducing gene called RAS. Abnormally low
levels of let-7 have been found in some types of tumor, said Sharp.



Sharp and MIT biology graduate student Margaret Ebert, lead author of
the paper, decided to block microRNA activity by creating a gene that
produces microRNA sponges and inserting it into their target cells.
Each sponge can bind up to six microRNA molecules, but they could be
engineered to bind more.



The sponge gene also includes a "reporter" gene that causes the cell
to become fluorescent if it has taken up the gene, so the researchers
can know for sure whether the microRNA sponge is being produced in a
particular cell.



Ebert said the new sponge technique is an improvement over an older
method that involves blocking microRNA activity with artificially
synthesized strands of RNA, known as oligos. One advantage is the
inclusion of the reporter gene; another is that the sponge genes can
be expressed continuously, while oligos do not remain in the cell
forever.



More importantly, the sponge technique could be used to create
transgenic animals that express the sponge in all of their cells,
allowing researchers to study microRNA function at the organismal
level. With such animals, sponge genes could be designed so that the
researchers can control when and where they are expressed.



Joel Neilson, a postdoctoral associate in the Center for Cancer
Research, is also an author on the paper. The research was funded by
the National Cancer Institute, the National Institutes of Health, a
Howard Hughes Medical Institute Predoctoral Fellowship, a Paul and
Cleo Schimmel Scholarship, and the Cancer Research Institute.



The MIT Center for Cancer Research (CCR) was founded in 1974, and is
one of eight National Cancer Institute-designated basic research
centers. Its mission is to apply the tools of basic science and
technology to determine how cancer is caused, progresses and responds
to treatment.


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Women's Advocates Call On The IOM To "Seize This Historic Opportunity" To Help Millions Of Women Suffering From Neglected Chronic Pain Disorders

Today, leading women's health advocates called on the Institute of Medicine (IOM), through the release of the first Congressionally-mandated report on the state of our nation's effort to eradicate chronic pain, to "seize this historic opportunity" to help the millions of afflicted American women suffering from prevalent, longtime neglected pain disorders.



In a letter sent today to Dr. Phillip Pizzo, Chair of the IOM Committee on Advancing Pain Research, Care and Education, organizational leaders of the Campaign to End Chronic Pain in Women thanked the IOM for their important work and called on the special Committee to be bold in its recommendations, which are expected by the end of June. The letter notes that up to 50 million women in America suffer from one or more of the following prevalent, neglected and poorly understood chronic pain conditions that frequently co-occur and disproportionately affect women: chronic fatigue syndrome, endometriosis, fibromyalgia, interstitial cystitis, TMJ disorders and vulvodynia, at an annual cost of up to $80 billion a year.



They called on the IOM to recommend a concerted and coordinated effort to confront this costly problem: "The report should call on our nation's leaders to enact a long overdue, concerted, coordinated, and serious effort to tackle this costly problem through an expanded collaborative research effort and improved clinical care. Doing so has the potential to not only lead to an improved quality of life for millions of Americans, but will start the process of reducing wasteful and inefficient health care spending."



Last year Congress directed the IOM to develop recommendations on how to significantly improve the state of our nation's pain research, medical management and educational efforts. This report is expected to be delivered to Congress by June 30, 2011. Since the IOM study began in November 2010, the Campaign has, on every available opportunity, submitted oral and written testimony; today's letter outlined essential elements of the solution to this complex problem.



"Through the release of this report, the IOM has a historic opportunity to redefine how our nation confronts our chronic pain epidemic," said the Campaign leaders. "These recommendations hold the promise of stimulating long-overdue improvements in the quality of medical care provided to millions of chronic pain sufferers."



Source:

Campaign to End Chronic Pain in Women

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Gene Abnormality Found To Predict Childhood Leukemia Relapse

Scientists have identified mutations in a gene that predict a high likelihood of relapse in children with acute lymphoblastic leukemia (ALL). Although the researchers caution that further research is needed to determine how changes in the gene, called IKZF1 or IKAROS, lead to leukemia relapse, the findings are likely to provide the basis for future diagnostic tests to assess the risk of treatment failure. By using a molecular test to identify this genetic marker in ALL patients, physicians should be better able to assign patients to appropriate therapies.


The findings of the Children's Oncology Group (COG) study, led by scientists from St. Jude Children's Research Hospital, Memphis, Tenn., the University of New Mexico Cancer Research and Treatment Center, Albuquerque, N.M., and the National Cancer Institute (NCI), part of the National Institutes of Health, appear online January 7, 2009, in the New England Journal of Medicine, and in print on January 29, 2009.


ALL, a cancer of the white blood cells, is the most common childhood cancer, in that it affects about one in 29,000 children annually. Using currently available therapies, cure rates for ALL are now upwards of 80 percent. However, those therapies carry with them substantial side effects, and even with treatment, only 30 percent of children who experience a relapse of ALL will survive five years. Determining the risk of relapse faced by an individual patient would help physicians tailor treatment intensity appropriately, but until now there has been no good marker for predicting outcome.


"Great progress has been made in recent years in improving the cure rate of childhood ALL," said Stephen Hunger, M.D., chairman of the COG ALL committee and the lead COG investigator on this study. "The findings of this study help us further subdivide those patients who are unlikely to be cured, and identify patients in whom different therapies should be tested."


In the study, researchers analyzed genetic data on leukemia cells obtained at diagnosis from 221 children with high-risk leukemia (i.e. a high chance of relapse) who had been treated in an existing COG study. They conducted their analysis using microarrays and DNA sequencing -- technologies which allow researchers to quickly and efficiently identify and analyze multiple genes simultaneously in the same cell. Using these technologies to identify genetic abnormalities in leukemia cells, the investigators examined the DNA of the leukemia cells at the time of diagnosis and then determined if any of the identified genetic changes predicted relapse. To confirm that specific genetic changes were associated with relapse, the scientists also examined a second group of 258 children with ALL who were treated at St. Jude.















"We looked across the genome in an unbiased fashion in an attempt to pull out any genes that were significantly associated with outcome," said Charles Mullighan, M.D., Ph.D., assistant member in the St. Jude Department of Pathology and the paper's first author. "From these findings, we identified a group of genetic abnormalities that together predicted poor outcome."


The most significant association was with the deletions or changes in the IKAROS gene. Mutations of IKAROS were shown to identify a subgroup of patients who were treated in the COG study that had a very poor prognosis. The prognostic significance of these genetic alterations was validated in the independent St. Jude patient group, a finding of particular importance since different types of therapies were used in these two groups of patients.


Previous research has shown that the IKAROS gene serves as the blueprint for the production of the IKAROS protein, which regulates the activity of many other genes. The IKAROS protein plays an essential role in the development of lymphocytes, the white blood cells that, when changed, give rise to pediatric ALL. The way in which IKAROS abnormalities contribute to the development of relapse remains to be determined.


The study also examined gene expression in the leukemia cells using microarray chips, and found that leukemia cells from patients with IKAROS alterations expressed primitive, stem cell-like genes, suggesting that the cells are less mature and possibly more resistant to the effects of drugs used to treat ALL. "These findings show how detailed analysis of leukemic cells using complementary techniques can enhance our understanding of the genetic basis of leukemia," said co-author Cheryl Willman, M.D., director and CEO, University of New Mexico Cancer Research & Treatment Center.


The researchers also tested whether the presence of IKAROS alterations was associated with levels of minimal residual disease, another measure of treatment response in ALL.


"Measurement of levels of minimal residual disease is widely used to monitor treatment responsiveness and also to alter patients' therapy if they have a very poor response to treatment," said James Downing, M.D., St. Jude scientific director and the paper's senior author. "An important analysis we conducted was to see whether identifying the association of IKAROS alterations with poor outcome added anything to just measuring levels of minimal residual disease. And, indeed, it did."


The researchers' analysis indicated that identifying IKAROS alterations may be clinically useful and will complement existing diagnostic tests and measurement of minimal residual disease levels.


While a clinical test for alterations of IKAROS could prove valuable for predicting poor outcomes in children with ALL, complexities remain. There are different types of deletions in the gene, some that involve the entire IKAROS gene and others that involve only parts of the gene. Because the genetic alterations in IKAROS in ALL are not uniform or limited to a single mutation or deletion, it may be necessary to develop a panel of different tests to detect IKAROS lesions and identify which patients are at highest risk for relapse.


This research was done as part of the NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative, which seeks to utilize the study of genomics to identify therapeutic targets in order to develop more effective treatments for childhood cancers. The first two cancers being studied in the program are ALL and neuroblastoma, a cancer that arises in immature nerve cells and affects mostly infants and children. Combined, these two cancers account for 3,000 new cases each year, and in both cancers, there are some children who have a very favorable prognosis and others who are at high risk for treatment failure. By determining the genetic factors that distinguish these groups, the hope is that researchers can use this information to improve patient outcomes and develop better treatments, particularly for those in the high-risk group.


"In the long term, our goal is to develop effective therapeutic interventions, directed toward vulnerabilities that leukemia cells acquire as a result of the genomic abnormalities identified through the TARGET initiative," said Malcolm Smith, M.D., Ph.D., of NCI's Cancer Therapy Evaluation Program. These are the first results to come out of this initiative. For more information about TARGET, please visit targetncer


Reference: Mullighan CG, Su X, Zhang J, Radtke I, Phillips LAA, Miller CB, Ma J, Liu W, Cheng C, Schulman BA, Harvey RC, Chen I, Clifford RJ, Carroll WL, Reaman G, Bowman WP, Devidas M, Gerhard DS, Yang W, Relling MV, Shurtleff SA, Campana D, Borowitz MJ, Pui C, Smith M, Hunger SP, Willman CL, Downing JR, and the Children's Oncology Group. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia. NEJM. Vol. 360, No. 5.


St. Jude Children's Research Hospital


St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. For more information, please visit stjude.


The Children's Oncology Group/CureSearch


Children's Oncology Group (COG), the world's largest cooperative pediatric cancer research organization, which includes every recognized pediatric cancer program in North America, comprises a network of more than 5,000 physician, nurse, and other clinical and laboratory investigators whose collaboration in clinical and translational research has turned childhood cancer from a virtually incurable disease to one with an overall cure rate approaching 80%. COG is committed to conquering childhood cancer through scientific discovery and compassionate care. For more information, please visit childrensoncologygroup.


The University of New Mexico Cancer Research and Treatment Center


The UNM Cancer Center is New Mexico's only National Cancer Institute-designated cancer center, and is home to the state's largest and most experienced team of cancer experts with 81 board-certified oncology physicians and more than 120 research scientists, supported by more than $50 million in grants annually. As the Official Cancer Center of the State of New Mexico, the Center served 7,600 new patients last year in 84,000 patient visits, treating nearly half of all adults with cancer in the state and virtually all the children.


The National Cancer Institute


NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers.


St. Jude Children's Research Hospital

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Ongoing Training In CT Colonography Recommended For Gastroenterologists

Recognizing that CT colonography will play a role in screening for colorectal cancer (CRC), and the critical need to increase overall CRC screening rates, the American Gastroenterological Association (AGA) Institute issued minimum standards for gastroenterologist performance of the test. To ensure competence, a minimum of 75 endoscopically confirmed cases should be interpreted by the physician.



Despite the fact that CT colonography has not yet been endorsed as a primary screening test in asymptomatic, normal risk adults, many patients have shown interest in this test. The indications for CT colonography are controversial, with many payers recommending that this test only be indicated for patients who have had a failed optical colonoscopy or who have a mass obstructing the colon where examination of the entire colon is required prior to surgical resection. Nonetheless, CT colonography may be considered for patients unwilling to undergo other colorectal screening tests, note the authors of the standards paper, which is published in Gastroenterology, the official journal of the AGA Institute.



"Because of our specialized training, gastroenterologists are experts in CRC screening and colorectal disease. It follows that if patients want a 'virtual colonoscopy' it may be highly appropriate to see a qualified gastroenterologist for the test," notes Don Rockey, MD, AGAF, chair of the AGA Institute Task Force on CT Colonography. "As CT colonography technology is evolving, it is important to check that your physician has been properly trained to ensure that the test is performed and interpreted accurately."



After formal training, during which at least 75 tests should be interpreted, the AGA Institute Task Force on CT Colonography, which authored the standards paper, recommends that gastroenterologists should participate in a mentored CT colonography preceptorship with the candidate physically present and involved in the interpretation of at least 25-50 additional cases. In addition, it is expected that those performing CT colonography will undertake ongoing training and self assessment including attending formal continuing medical education-accredited courses in CT colonography.



The AGA Institute Task Force on CT Colonography offers the following recommendations. The full recommendations are available in the September issue of Gastroenterology.



Patient Care


* Any polyp > 6 mm in size (i.e., widest diameter) should be reported and the patient referred for consideration of endoscopic polypectomy.


* Patients with three or more polyps of any size in the setting of high diagnostic confidence should be referred for consideration of endoscopic polypectomy.


* The appropriate clinical management of patients with one to two lesions no greater than 5 mm in diameter is unknown. In the absence of data, the follow-up interval recommended for these patients should be based on individual characteristics of the patient and procedure.
















Quality Control and Safety


* Practices offering CT colonography should establish a technical quality control program.


* Endoscopic results in patients referred from CT colonography to endoscopy, including true positive and false negative rates, should be tracked.



Regulatory Issues


* Split interpretations of CT colonography are feasible.


* Gastroenterologists and radiologists performing split interpretations should dictate and sign separate procedure reports that clearly state the specific services they performed related to CT colonography.



Exam and Equipment Specifications


* CT colonography should be performed using multidetector CT protocols with high spatial resolution.


* Computer workstations for dedicated CT colonography interpretation should permit 2D and 3D correlation and visualization of the colonic lumen.


* CT colonography images should be archived for later comparison.


* Primary 2D or primary 3D review of the endoluminal surface of the colon and rectum is required.



Guidelines from multiple agencies and professional societies, including the AGA Institute, underscore the importance of colorectal cancer screening for all individuals 50 years of age and older (younger for certain groups known to be at higher risk). The U.S. Preventive Services Task Force, the U.S. Multi-Specialty Task Force, and others have published recommendations for screening for colorectal cancer, the second-leading cause of cancer deaths in the United States. Currently, recommended screening tests include colonoscopy, flexible sigmoidoscopy, barium enema, and fecal occult blood tests.



The AGA Institute formed the CT Colonography Task Force to develop minimum training standards for gastroenterologists in order to provide guidance, and to ensure minimum training competencies are upheld for the performance of the exam. The AGA Institute continues to monitor CT colonography along with other potential colorectal cancer screening tests, and will continue to develop guidance tools and reports as appropriate. The AGA Institute will host a course on CT colonography for gastroenterologists on March 7-8, 2008, in Washington, DC. Additional information will be available this fall.







About the AGA Institute


The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is one of the oldest medical-specialty societies in the United States. Comprised of two non-profit organizations -- the AGA and the AGA Institute -- our more than 16,000 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, while the AGA Institute, a 501(c3) organization, runs the organization's practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization's annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. For more information, please visit gastro/.



About Gastroenterology


Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top one percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, CABS, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit gastrojournal/.



Source: Aimee Frank


American Gastroenterological Association

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How A Well-Known Epilepsy And Pain Drug Works

A Duke University Medical Center researcher who spent years looking for the signals that prompt the brain to form new connections between neurons has found one that may explain precisely how a well-known drug for epilepsy and pain actually works.



The finding may also point to new therapies for brain injury and neuropathic pain.



The role of neurons in the brain and nervous system is well known, but astrocytes, a different type of brain cell, still are largely a mystery. Duke scientist Cagla Eroglu, Ph.D. has discovered a receptor that receives messages from astrocytes so that the brain can form excitatory synapses, the cell-to-cell connections that can become overactive in conditions such as epilepsy. Working with a team of scientists from other institutions, Eroglu found this receptor is also blocked by the anti-convulsant drug gabapentin (Neurontin™).



The study will appear in the Oct. 16 issue of Cell.



"The study links astrocytes and their role in synapse formation to diseases, so if the normal process goes wrong, this may explain why people get epilepsy, why epilepsy gets worse, or why they have neuropathic pain," said Eroglu, assistant professor in the Duke Department of Cell Biology. "It's a fine balance, because synapse formation has to occur during development for neurons to transmit brain signals, but if this happens in an uncontrolled manner in the adult brain, it could lead to these debilitating conditions."



Eroglu spent years looking for this neuronal receptor, which prompts synapse formation. "The key clue came when we chopped thrombospondin, a protein that comes from astrocytes and triggers establishment of synapses, into small fragments and put it onto neurons. We found that a specific portion of thrombospondin, the EGF-like domain, was equally effective as the whole protein. This gave me the clue that was necessary to identify its neuronal receptor. However it took me a while to do so."



On advice she heard from a lecture by another scientist, Nobel laureate Linda Buck - "Spend more time thinking about your experiments and your results before designing new experiments" - Eroglu took a short break from her bench-work, went home, and reasoned her way through several possibilities, finally settling on the idea that a receptor for the molecule gabapentin might be a key to regulating the formation of synapses. Excited, she returned to the lab and verified the interaction between proteins. "When I discovered that gabapentin completely blocked synapse formation between isolated neurons, I could not sleep for days until I replicated the results."



The research also points to the need for further research on gabapentin's actions, Eroglu said. The drug gabapentin strongly blocks the receptor, reducing synapse formation in rodents.
















"The question is whether gabapentin might be linked with or interfere with cognitive ability, especially in the developing fetus of a woman taking the drug to control epilepsy," Ergolu said. "But of course this needs to be balanced with the mother's need to prevent her from having seizures."



"Likewise, while it is rare that a young child is given gabapentin for seizures, I think scientists need to study whether this possibly could be linked with side effects of this drug in children such as hyperactivity, irritability and maybe even cognitive problems," she said.



Gabapentin may also be a boon for certain conditions that haven't yet been studied, she said. For example, in soldiers who have severe head wounds, many go on to develop epilepsy in the months after their injuries. "Maybe their injuries trigger the development of excess excitatory synaptic connections, and blocking or modulating this preemptively with gabapentin could help to prevent in this situation."



She said that understanding how the receptor works could also help patients who have neuropathic pain because of advanced diabetes or an injury.



"Neuropathic pain is not perceived by patients in the same way as other types of pain." Eroglu said. "Regular anti-analgesic drugs do not successfully ease this type of pain. Based on our findings it is possible that aberrant new synaptic connections that occur after injury contribute to neuropathic pain, and gabapentin might work by breaking this cycle of synapse formation."



The research was supported by grants from the National Institute of Drug Addiction, the National Heart, Lung and Blood Institute, the National Institutes of Health, the Human Frontiers Scientific Program long-term fellowships, and the Helen Hay Whitney postdoctoral fellowship.



The senior author of the work is Dr. Eroglu's mentor Ben A. Barres, of the Department of Neurobiology at Stanford University School of Medicine in Stanford, Calif.,. Other authors include Nicola J. Allen, Michael W. Susman, Chan Young Park, Chandrani Chakraborty, Sara B. Mulinyawe, Andrew D. Huberman, Eric M. Green, and Ricardo Dolmetsch, of the Stanford Department of Neurobiology; Jack Lawler, of the Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School in Boston; Nancy A. O'Rourke, Engin Ozkan, K. Christopher Garcia, and Stephen J. Smith, all of the Department of Molecular and Cellular Physiology at Stanford (Ozkan and Garcia are also in the Stanford Department of Structural Biology and Howard Hughes Medical Institute); Z. David Luo, of the Department of Anesthesiology & Perioperative Care, University of California, Irvine; Arnon Rosenthal, of MazoRx Inc., Redwood City, Calif.; and Deane F. Mosher and Douglas S. Annis of the Department of Medicine, Medical Sciences Center, University of Wisconsin, Madison.



Source:
Mary Jane Gore


Duke University Medical Center


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European Medicines Agency Publishes First Weekly Pandemic Pharmacovigilance Update

The European Medicines Agency has published today the first in a series of weekly pandemic pharmacovigilance updates.


These weekly bulletins will provide information on adverse reactions reported after the use of centrally authorised pandemic influenza vaccines and antivirals in the European Union and complement the information the Agency has been publishing regularly on the development and approval of medicines for use during the pandemic.


"I am confident that the weekly updates will allow to further increase transparency in the field of pandemic and to provide up to date information in a timely manner to the public," said Thomas L?¶nngren, Executive Director of the European Medicines Agency.


This information will support European institutions and Member States in their communications, and provide an additional resource when recommending the use of vaccines and antiviral treatments.


The information on adverse reactions in the update comes from EudraVigilance, the central European database on adverse reactions, managed by the Agency. It is based on reports from Member States and marketing authorisation holders.


The weekly update also provides an estimate of how many doses of pandemic vaccines and antivirals have been administered in the European Union, and other information that helps put adverse reaction reports in context.



Notes


1. The update can be found here.


2. There are three pandemic vaccines, Celvapan, Focetria and Pandemrix, authorised by the European Commission, and one antiviral, Tamiflu. There are other pandemic vaccines and antivirals approved by Member States. Information on the Agency's activities in relation to the influenza pandemic can be found on the Agency's Pandemic influenza (H1N1) website.

Source
European Medicines Agency


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Breast Cancer - Diagenic Announces Launch Of First Breast Cancer Gene-Expression Blood Test

DiaGenic ASA (OSL: DIAG) and Applied Biosystems Inc. (NYSE: ABI) today
announced the launch of BCtect(TM), a blood-based test for early detection of
breast cancer. The test searches for a unique gene expression signature
identified by DiaGenic using a custom TaqMan(R) Array manufactured for
DiaGenic by Applied Biosystems. India was chosen as the first country for the
introduction of BCtect(TM) after successful completion of a large study in
the country.





The DiaGenic BCtect(TM) test addresses a significant medical need in
India, where breast cancer is the second leading cause of death among women.
The lack of a coordinated national screening program means that breast cancer
is typically detected at a late stage, resulting in high mortality rates
compared to Western countries. Last year alone, nearly 100,000 women in the
country died from the disease. Breast cancer is also on the rise, with an
estimated 250,000 new cases expected in India by 2015. A key problem has been
the detection of only 10% of cases at an early stage, which lags far behind
Western countries where detection rates reach as high as 65%.





Studies show there is more than a 90% chance of surviving breast cancer
if detected at an early stage, whereas the mortality rate reaches 90% if this
disease is caught at a very late stage. Clinical studies performed on a group
of Indian women by DiaGenic have shown that the test can detect tumors early
and accurately, in particular among younger (pre-menopausal) women and those
with dense breasts.





DiaGenic launched BCtect(TM) at a special event in New Delhi. Speaking at
the launch, DiaGenic CEO Erik Christensen, M.D. Ph.D., said that the company
decided to launch the test in India because of the interest generated by its
large clinical study across the country, which confirmed the test's gene
signature is unaffected by ethnic variation.





"We hope that by introducing a test that uses peripheral blood rather
than tissue from the actual breast, more women will be encouraged to come
forward for testing," said Dr. Christensen. "In addition, we see BCtect(TM)
filling a gap where mammography is not readily available."





More details on the selection of India as the first market for the new
product were given by Praveen Sharma, Ph.D., co-founder of DiaGenic. "The
results from our Indian study showed that the gene set, previously identified
in Scandinavian and US cohorts, also had similar good diagnostic and
predictive performance in the Indian population. BCtect(TM) is not affected
by ethnic variation or menopausal state of the patient, allowing for
widespread use to diagnose breast cancer at an early stage."





The TaqMan Array manufactured for DiaGenic by Applied Biosystems consists
of 96 TaqMan(R) Gene Expression Assays pre-loaded multiple times on a
384-well micro fluidic card. These 384 simultaneous real-time PCR reactions
are performed without the need to use liquid-handling robots or multichannel
pipettors. The array is run on the Applied Biosystems 7900HT Fast Real-time
PCR System by Labindia.





"We continue to demonstrate our commitment to providing scientists with
the molecular tools they need to develop important diagnostics," said Peter
Dansky, president of Applied Biosystems' functional analysis division.





"The TaqMan Arrays provide an ideal format for surveying gene expression
markers based in their easy-to-use format, high sensitivity, and ability to
facilitate standardization among laboratories for consistent and reliable
results."





The DiaGenic BCtect(TM) breast cancer test will be marketed in India
through Religare SRL (formerly known as SRL Ranbaxy), the largest laboratory
chain in South East Asia. Sanjeev K. Chaudhry, M.D, CEO of SRL predicts high
demand for the DiaGenic test.





"We believe that BCtect(TM) will provide the perfect incentive for women
to take charge of their health and undergo regular check-ups," said Dr.
Chaudhry. "Religare SRL will put in place intensive and extensive
market-facing strategies to ensure rapid growth in the market, both locally
and internationally, and will invest substantial amounts and efforts to
inform the market on the availability of this new innovative test."




The DiaGenic BCtect

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Citigroup's H. Allen Bouch And Stanford's Kuldev Singh, MD Elected To Glaucoma Research Foundation Board Of Directors

H. Allen Bouch, Managing Director of Citigroup Global Markets, and Kuldev Singh, MD, MPH, Director of the Glaucoma Service at Stanford University, were elected to the board of Glaucoma Research Foundation, GRF President and CEO Thomas M. Brunner recently announced.


"We are deeply grateful to be able to attract this kind of top flight leadership to our board," said Brunner. "There is an impending epidemic of blindness looming from glaucoma unless we can get ahead of it with research and education," explained Brunner, "and people like Mr. Bouch and Dr. Singh who make this their top priority are essential to the ultimate success of our efforts."


Brunner was especially appreciative of efforts both new board members have already made to GRF's cause of speeding the cure and spreading the word. "Allen galvanized everyone's efforts last year," Brunner said, "to establish our first-ever benefit event which, under his co-chairmanship, exceeded all our expectations. He established our benefit as a 'can't miss' gathering for leaders in the philanthropic, scientific, medical, business and social communities." Based in San Francisco, H. Allen Bouch co-heads Citigroup's West Coast investment banking business. Among other responsibilities, Allen manages many of Citigroup's most important corporate relationships. He has a BA degree from Claremont McKenna College and an MBA degree from Duke University. Bouch and his wife, Lori, have three children and live in Piedmont, California.


"Dr. Singh has long been regarded as one of our regions leading glaucoma experts, and his efforts to help establish our new Silicon Valley chapter have been highly motivating," Brunner said. At Stanford, Singh has served as the Director of the Glaucoma Service for 15 years. He served as one of four advising deans at Stanford from 2002-2005 and received the 2006 Franklin Ebaugh Award for advising medical students and service to the Stanford University School of Medicine. Singh received his medical degree from The Johns Hopkins University School of Medicine and a Master of Public Health Degree from the Department of Epidemiology at Johns Hopkins.


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GOP Sens. Say Sotomayor Filibuster Possible But Unlikely, Obama Defends Judge's Past Comments

Several Republican senators in appearances on various talk shows on Sunday said that they do not expect the GOP to attempt a filibuster to block the Supreme Court nomination of Judge Sonia Sotomayor, although none ruled the idea out, the Washington Post reports. Sen. Kay Bailey Hutchison (R-Texas) said that she does not think the "need for filibuster will be there unless we have not had a chance to look at the record fully," adding that the Senate "need[s] to look at the record fully" and in an "expeditious way." Sen. Jeff Sessions (R-Ala.), the ranking member on the Senate Judiciary Committee, on NBC's "Meet the Press" said that Sotomayor's 17-year career as a federal judge is "very strong in her favor" and "the kind of background you would look for" in a Supreme Court justice. However, Sessions added that he and other Republican senators are concerned over a remark Sotomayor made in 2001 at a conference on Hispanics in the judiciary. According to the Post, Sotomayor was discussing how her Puerto Rican heritage has influenced her role as a judge when she said, "I would hope that a wise Latina woman with the richness of her experience would, more often than not, reach a better conclusion than a white male who hasn't lived that life." Sessions said the remark "goes against the heart of the great American heritage of an independent judge" (Barnes, Washington Post, 6/1). Judiciary Committee member John Cornyn (R-Texas), appearing on ABC's "This Week," said that senators "need to know ... whether she's going to be a justice for all of us or just a justice for a few of us" (Wallsten, Los Angeles Times, 6/1).

Sen. Charles Schumer (D-N.Y.) -- Sotomayor's sponsor through the confirmation process -- said on "This Week" that she is "virtually filibuster-proof when people learn her record and her story." He added that Sotomayor is "legally excellent" and "not a far-left-wing judge" (Barnes, Washington Post, 6/1).

White House Defends Sotomayor's Comments

White House Press Secretary Robert Gibbs said that he thinks Sotomayor would "say that her word choice in 2001 was poor, that she was simply making the point that personal experiences are relevant to the process of judging." In an interview with NBC News that will air this week, President Obama also defended Sotomayor, saying that "if you look in the entire sweep of the essay that she wrote, what's clear is that she was simply saying her life experiences will give her information about the struggles and hardships that people are going through" (Eggen/Kane, Washington Post, 5/30).














Obama also stood by his decision to nominate Sotomayor in his weekly radio and Internet address on Saturday. Obama said that he is "certain that she is the right choice" and that her record as a federal judge "makes clear that she is fair, unbiased and dedicated to the rule of law." While he said he expects "rigorous evaluation" of Sotomayor, Obama said his "hope is that we can avoid the political posturing and ideological brinkmanship that has bogged down this process, and Congress, in the past" (AP/USA Today, 6/1).

First Meetings With Senators Expected This Week

According to the AP/Chicago Tribune, Sotomayor is scheduled to hold her first meetings with senators this week, beginning on Tuesday with Sessions and Democratic Sens. Harry Reid (Nev.) and Judiciary Committee Chair Patrick Leahy (Vt.). Gibbs said a meeting with Senate Minority Leader Mitch McConnnell (R-Ky.) also is possible, adding that he is hopeful there will be other meetings scheduled throughout the week (AP/Chicago Tribune, 5/31).

The Wall Street Journal reports that the formal Senate confirmation hearings are not expected to begin for several weeks. The White House would like the Senate to confirm Sotomayor before the August recess so she will be on the bench for the court's next term, which begins in October. Although some GOP senators say this might not be enough time to fully examine her record, Sotomayor is expected to be confirmed, the Journal reports (Bendavid, Wall Street Journal, 6/1).


New York Times Editorial Urges Critics To 'Elevate the Discussion' on Sotomayor

A New York Times editorial says a majority of the issues conservatives are raising against Sotomayor are "not among" those on which she needs to be vetted. Sotomayor is "being called racist" and "attacked as not smart enough, as too abrasive," the editorial states, adding, "It is time to elevate the discussion to where it belongs: the Constitution and the role of the judiciary." The editorial continues, "Despite her long service as a federal judge, [Sotomayor's] record on many important issues is sparse," including her views on the right to privacy, "a critical doctrine that provides the basis for abortion rights." Nominees to the Supreme Court "should not go into specifics about cases they might judge," but the Senate in recent years "has allowed them to be far too opaque about their broader views on the Constitution and judging," the editorial says. Republican elected officials and conservative groups "see this nomination as a way to score points off wedge issues that excite their base," the editorial states, concluding, "It diminishes everyone when a nomination process deteriorates into character assassination and ethnic intolerance" (New York Times, 5/31).


Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women's Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women's Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.


© 2009 The Advisory Board Company. All rights reserved.

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mtm's P16/Ki-67 Dual Immuno-Staining Identifies High-Grade Cervical Disease In ASC-US And LSIL With High Sensitivity And Specificity

mtm laboratories, a privately held diagnostics company developing, manufacturing and globally commercializing in vitro diagnostics for cervical cancer early detection and diagnosis, today announced the publication of a new paper showing that dual staining for p16 and Ki-67 can pinpoint the underlying high-grade cervical disease with a high degree of sensitivity and specificity in women with ASC-US or LSIL cytology results. These are a group of patients currently poorly served by existing screening technologies, with too many referred for unnecessary colposcopy. The paper, which details the EEMAPS study results, has been published electronically in Cancer Cytopathology on March 25, 2011 ahead of print.


The EEMAPS study used the advanced biomarker combination CINtec® PLUS, which was launched by mtm in early 2010 in Europe. Residual materials from a previous pan-European retrospective cytology study were used to prepare additional slides for p16 and Ki-67 dual immuno-staining. In total, 361 ASC-US and 415 LSIL cases with corresponding biopsy results and HPV test results were available for dual stain cytology analysis. The presence of one or more dual-stained cervical epithelial cell(s) defined a positive test result with CINtec® PLUS, independent from morphology interpretation. The clinical results showed that the sensitivity of the dual stain for high-grade disease was 92.2% (71/77) for ASC-US, and 94.2% (129/137) for LSIL cases, which is equivalent to the sensitivity results obtained for HPV testing. However, specificity was significantly higher for CINtec® PLUS as compared to HPV testing; 80.6% vs. 36.3% for ASC-US and 68.0% vs. 19.1% for LSIL.


"mtm's CINtec® PLUS is the first test that provides high sensitivity and high specificity for underlying high-grade cervical disease in a single product, irrespective of women's age and the individual HR-HPV genotype," commented Bob Silverman, CEO of mtm laboratories. "Because the test can pinpoint which women are most likely to have cervical disease and need follow up, this should reduce a large number of the unnecessary, uncomfortable and costly colposcopies carried out on women with ASC-US or LSIL."


ASC-US and LSIL are definitions for equivocal and mild to moderate abnormal cytology findings on Pap tests, and may represent 5-8% of all cervical cytology cases. While most of these findings are negative for high-grade disease, 15-20% of LSIL and 6-10% of ASC-US will harbour high-grade disease. Together, these two categories of cytology represent the source for about 60% of all cases of high-grade cervical disease in women. Unfortunately, these Pap cytology results are not adequate predictors in determining which ASC-US or LSIL cases require intervention due to the low rates of underlying disease. Adjunctive HPV testing also has limitations due to unsatisfactory specificity.


The title of the publication and the authors are as follows:















Schmidt D, Bergeron C, Denton KJ, Ridder R, for the European CINtec Cytology Study Group. p16/Ki-67 Dual-Stain Cytology in the Triage of ASCUS and LSIL Papanicolaou Cytology. Cancer Cytopathol (2011); 119, DOI: 10.1002/cncy.20140


Notes


CINtec® PLUS


CINtec® PLUS is a screening and diagnostic tool combining high sensitivity and high specificity for detecting high-grade cervical disease in a single test. The CINtec® PLUS kit detects and stains for two biomarkers: the multiply validated cell cycle regulatory protein p16INK4a (p16) and Ki-67, a marker of active cell proliferation. Clinical trials involving over 32,000 women have demonstrated that when used together, this biomarker combination is both highly sensitive and highly specific to identify those women most likely to have existing high-grade disease. Moreover, the CINtec® PLUS test is independent of age and HR-HPV type of infection.


Applied in combination the co-detection of p16 plus Ki-67 in the same cell serves as an indicator of cell cycle de-regulation that occurs during HR-HPV induced oncogenic transformation and provides an objective criterion to identify those women who are likely to harbour high-grade disease. CINtec® PLUS can be applied on conventional and liquid based cytology slides. Double immuno-reactive (or: Dual-stained) cells in cytology are positively stained for both proteins:


- Brown cellular staining indicates p16 over-expression

- Red nuclear staining indicates Ki-67 expression


Classification of Cervical Cytology


The Pap smear classifications are related to the nature of the cells sampled from the cervix showing single cells or groups of cells. The most recent classification is the Bethesda system, which divides the results of the morphologic interpretation into four main groups:


1) Cervical specimens negative for intra-epithelial lesions or malignancies (NILM) - cases with morphological interpretation within normal limits


2) Atypical Squamous Cells of Undetermined Significance (ASC-US) - cases with no definitive cellular abnormality but enough suspicion to keep the case from being considered "normal" (this is an ambiguous category)


3) Low-grade Squamous Intraepithelial Lesion (LSIL)


4) High-grade Squamous Intraepithelial Lesion (HSIL)


Broadly speaking LSIL corresponds to mild to moderate pre-cancerous disease and HSIL corresponds to high-grade pre-cancerous disease. Screening with cytology provides an indicator to the physician that something may be wrong with a woman's cervix and can be used to direct this patient towards further evaluation (eg colposcopy).


Source:

mtm laboratories AG

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The Environment In Which Our Genes Live Explored In New Journal

The composition of our DNA is not the only thing that determines how our genes behave. A new journal just launched by the open access publisher BioMed Central, Epigenetcs and Chromatin, will enable researchers at all levels to discuss the heritable changes that do not alter DNA sequence, but rather involve stable modifications of chromatin, DNA or protein conformation.



The journal's co-Editors-in-Chief, Steven Henikoff and Frank Grosveld, are excited about this field's potential. According to Henikoff, "The field of epigenetics is at an exciting stage, one that seems comparable to the field of genetics before the elucidation of the structure of DNA and the genetic code. We know most of the parts, but we are still unclear as to how they work together as a system to faithfully maintain gene expression states. As our understanding of epigenetic inheritance and chromatin-based interactions progresses, we expect that Epigenetcs and Chromatin will become a key scientific resource".



Articles in the first issue exemplify the type of high quality research that the journal will publish. A study by Elizabeth Blackburn, John Sedat and colleagues applies new methodology for 4D imaging to document a previously undescribed behavior of human telomeres. Another study by Neil Brockdorff and colleagues provides a comprehensive answer to a long-standing question of the role of the RNAi pathway in X inactivation.



Grosveld said, "I'm thrilled to be part of the launch, particularly because this is an open access journal that fulfils the need for a resource that reflects the breadth of epigenetic research. The positive response by colleagues around the world who have participated in this venture has been fantastic."







Notes:



1. All articles are available free of charge, according to BioMed Central's open access policy.



2. Epigenetcs and Chromatin is a peer-reviewed open access online journal, which will publish articles that provide novel insights into epigenetic inheritance and chromatin-based interactions. The journal's website is epigeneticsandchromatin/



3. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.



Source: Graeme Baldwin


BioMed Central

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Black Women In Virginia More Likely Than Others To Experience Infant Mortality

Black women in Virginia are two-and-a-half times more likely than women of other races to experience infant mortality, according to the state Department of Health, the Newport News Daily Press reports. In 2007 in Hampton, there were four deaths per 1,000 live births among white infants, compared with 12.7 deaths per 1,000 live births among black infants. Nationwide, the infant mortality rate among blacks in 2000 was 14.1 deaths per 1,000 live births, according to the Office of Minority Health and Health Disparities. The national average is 6.9 deaths per 1,000 live births.

The leading cause of infant mortality in Hampton Roads is premature birth, followed by sudden undetermined infant death, according to the Daily Press.

Research by Jerome Strauss, dean of medicine at Virginia Commonwealth University, has found a connection between the environment and a genetic variation that causes the fetal membrane to rupture, leading to pre-term births in black women. "That's a significant risk increase. That's not going to explain all pre-term births that occur in African-Americans, but it's going to be a factor that's responsible," he said.

Thursa Crittenden of the Virginia Department of Health's Office of Minority Health and Public Health Policy, attributes part of the disparity to chronic stress that black women face, which predisposes them to poor health.

Pamela Hammond, dean of Hampton University's School of Nursing, noted that biology, access to health care and socioeconomic issues also contribute to health disparities. "There is no one factor that causes this health disparity. It is multifactorial," she said (Kelly, Newport News Daily Press, 5/3).


Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

© 2009 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

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New Testing Now Available - Conceptions Reproductive Associates Of Colorado

To better serve our patients, Conceptions is now able to run out of our in-house lab a wide range of fertility laboratory tests, which means quicker turn-a-round time and consistency of lab results. Conceptions Laboratory and physicians are proud to participate with most major insurance plans. This is important as this means our patients will have the peace of mind of not paying any extra costs.


For the out-of-pocket paying patient, we offer cash pay and credit discounts to help lower the costs. We understand some insurance plans have contracts with outside laboratories; therefore, this means Conceptions is obligated to send those tests out to the appropriate laboratory.


Conceptions Laboratory also offers semen analysis, utilizing Kruger Strict Criteria. In addition, Conceptions offers sperm preparation intrauterine insemination (IUI), cryopreservation of sperm for pre-chemotherapy and pre-vasectomy. Conceptions will file with insurance for these services if patients have a benefit, otherwise the same cash pay and credit discounts apply.


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Conceptions Reproductive Associates of Colorado

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For Management Of Hyperuricemia In Patients With Gout, Uloric (Febuxostat) Demonstrated Efficacy

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Strong Evidence Of A Genetic Risk Factor For Parkinson's Disease

A Mayo Clinic-led international research collaboration -- one of the largest studies of its kind -- provides strong evidence that a genetic risk factor may account for 3 percent of the cause of Parkinson's disease.



Parkinson's disease is a debilitating neurological disease that affects about 1 million people in the United States. Little is known about its causes and hence there is no cure.



"This is an important step forward because the contribution of common genetic risk factors to the development of Parkinson's has long been suspected, but the high quality of data needed to make such discoveries has been missing," says Demetrius Maraganore, M.D., Mayo Clinic neurologist and lead study investigator. "This well-designed and large study provides evidence that common genetic variants contribute to the cause of Parkinson's."



The collaboration included researchers from 11 countries. Their findings will be published in the August issue of the Journal of the American Medical Association (jama.ama-assn/).



In their study, the researchers analyzed clinical and genetic data from 2,692 Parkinson's disease patients and 2,652 healthy subjects who were matched to the Parkinson's patients for age and gender. Results showed that persons with longer lengths of a DNA segment that promotes the activity of a gene known as alpha-synuclein had a 1.5 times greater risk for Parkinson's disease.



Explains Dr. Maraganore, "Our study provides compelling evidence that variability in the alpha-synuclein gene is a risk factor for Parkinson's disease worldwide. The common DNA variants that increase Parkinson's disease risk cause the gene to produce too much alpha-synuclein protein in a process known as overexpression. Our findings support the development of therapies that reduce alpha-synuclein gene expression. Such therapies have the potential to prevent or delay the onset of Parkinson's disease or to halt or slow its progression."



Significance of the Research



Earlier, small studies showed that rare variations (mutations) in the alpha-synuclein gene caused Parkinson's disease in a few isolated families. Further small studies suggested that common variations in the gene, while not sufficient to cause Parkinson's, make people susceptible to the disease.



"However, the results of those small studies were inconsistent," says Dr. Maraganore. "What was lacking was a well-designed, large study to see if common variations in the alpha-synuclein gene contribute to Parkinson's risk worldwide. The current study provides this much-needed evidence. Alpha-synuclein gene variability was associated with Parkinson's disease across several populations."







About Parkinson's Disease

Parkinson's disease involves the degeneration of brain cells, particularly those that make the chemical dopamine. The disease is characterized by uncontrolled shaking (tremor), slowed movements, muscle stiffness and imbalance. While available treatments can reduce the symptoms, their benefit is short-lived. No method can prevent Parkinson's or slow or halt its progression.



Collaboration and Support

Investigators from Mayo Clinic, other U.S. medical centers and from medical centers in 10 other countries, including Australia, Belgium, France, Germany, Greece, Italy, Ireland, Norway and Singapore, participated in this research. The work was supported primarily by an Edward J. Safra Global Genetics Consortium grant of the Michael J. Fox Foundation for Parkinson's Research.



Disclosure: In accordance with the Bayh-Dole Act of 1980, Dr. Maraganore and Mayo Clinic report U.S. and foreign pending patent applications for a technology that provides diagnosis and treats neurodegenerative diseases. Mayo Clinic has licensed this technology to Alnylam Pharmaceuticals, Inc., and both Mayo Clinic and Dr. Maraganore may receive royalties from that license. Additional disclosures are detailed in the JAMA paper.



To obtain the latest news releases from Mayo Clinic, go to mayoclinic/news. MayoClinic (mayoclinic/) is available as a resource for your health stories.



Contact: Lisa Lucier

Mayo Clinic

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People With Chronic Pain Face Complex Dilemmas And Life-changing Decisions

Coping with chronic pain can affect every aspect of a person's life and cause conflict between what their mind wants to achieve and what their body allows them to do, according to research in the December issue of the Journal of Nursing and Healthcare of Chronic Illness.


Swedish researchers carried out in-depth interviews with ten people who had experienced chronic pain for between four and 32 years and were taking part in an outpatient rehabilitation programme. Nine of the patients, who ranged from 22 to 50 with an average age of 38, were unable to work because of their pain.


"A recent research study found that chronic pain affected up to 30 per cent of adults across Europe, impacting on people's everyday lives and in many cases their ability to work" says lead author Asa Skjutar from the Karolinska Institutet.


"Although multidisciplinary rehabilitation programmes for people with chronic pain are well established in Sweden, they don't work for everyone. There can be a number of reasons for this, from failing to customise treatment to individual needs through to delayed intervention which makes people less amenable to change.


"What is clear is that many patients with chronic pain find that their needs are not being met by healthcare professionals. Previous research has found that patients' beliefs play an important role in how successful any interventions are. That is why we were keen to find out how people felt chronic pain impacted on their lives."


Three key themes emerged during the interviews:


Adapting


Patients expressed conflicts between what they wanted to do and what their body let them do and they were constantly weighing up the consequences of their actions.


One woman described how she had to set her pain aside, grit her teeth and let her mind take the lead as she got her children off to school and daycare. "Had I listened to what hurts, then I wouldn't have done it" she said. Another patient talked about how a fishing trip satisfied his lust for adventure, even though he was aware of the increased pain that might follow.


Others, however, talked about not making definite plans to avoid the guilt of cancelling. They also said that they had no problem in accepting help or stopping what they were doing if they felt their pain levels would escalate.


"The participants had gone though rehabilitation programmes that recommend a steady and moderate level of activity, but said that they had not found the best way to manage their pain" says Asa. "They moved between the two extremes of letting their body and their mind lead and repeated this cycle so that neither dominated."


Discovering


Patients also spoke about their need to let go of the way they used to live - including their behaviour, daily routines and independence - and find new ways to express themselves. "It's so strange for me to say no" said one participant. "I'm not used to it. Nobody else is used to it either." But she learnt how to say no and, although it was tough, it felt good.















Another patient talked about how he had managed to paint a wall on one side of the house, but was unable to paint the remaining walls. "I am very pleased that it looks so nice even though I know that the other ones aren't done" he said. "Before I wouldn't have looked at that wall, I would've looked at the other ones."


"These transformations didn't happen overnight, they happened bit by bit" says Asa. "But they made people realise that they had made the adjustments they needed to make to their lives to manage their pain."


Engaging


People who took part in the study also realised that they needed to manage their pain in order to enjoy their lives. They initially focused their energy on work-related roles and finding a fast cure for their pain, but this often led to more pain and feelings of defeat.


Family time and friendships became very important, because social interaction could often be achieved without too much activity. "I'm seeing friends and family again, which means a lot to me" said one participant. It was also important to have a change of scene. "I went to a friend's and played a video game and talked and just had a good time, just relaxed" said another. "It was so nice to get out and do something."


"Doing something they enjoyed gave people energy and made them feel more optimistic and positive" says Asa.


"Understanding how people are affected by chronic pain enables healthcare professionals to give them the support they need to adapt their lives, discover a new way forward and engage with friends and family in a way that enhances their quality of life" she concludes.


"Chronic pain is a very common health problem in adults and its management affects not just people's personal lives and relationships but their contribution to society and the economy. It is vital that we enhance our understanding of people's needs so we can provide more effective chronic pain management services that meet people's varied and changing needs."


Sources: Wiley - Blackwell, AlphaGalileo Foundation.

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Ebbe Nielsen Prize For Developer Of DNA Barcode Database

Sujeevan Ratnasingham, the bioinformatics expert who developed the Barcode of Life Data Systems (BOLD) platform for the global DNA barcoding community, has won this year's Ebbe Nielsen Prize from the Global Biodiversity Information Facility (GBIF).



Ratnasingham is Informatics Director for the Biodiversity Institute of Ontario at the University of Guelph and informatics lead for International Barcode of Life (iBOL) project. He is the first Canadian winner of the €30,000 Ebbe Nielsen Prize, named for the late Danish entomologist who helped to create the Global Biodiversity Information Facility.



Ratnasingham's development of the BOLD system "is a major and innovative landmark in bringing genomic data on biodiversity to research and research applications for science and society," said Leonard Krishtalka, chair of the GBIF science committee. Established in 2001, the prize is given to a promising, early-career researcher using biosystematics and biodiversity informatics in novel ways.



"The prize acknowledges the value of genetic data to biodiversity science and recognizes the important work that Sujeevan and his colleagues have been doing," said iBOL Scientific Director Paul Hebert.



Ratnasingham has overseen the growth of BOLD into a system that combines barcode data with images and other information about species' genetic and morphological traits, geographical data and taxonomy. "The focus of my work is developing systems that allow many researchers to work together and share information on a global scale," said Ratnasingham.



Scientists use the system to enter, share and analyze information about hundreds of different barcoding projects around the world and to contribute to a barcode library that now contains hundreds of thousands of specimen barcodes from 70,000 species. "It's impossible to work with this volume and diversity of data without novel computing platforms," said Ratnasingham.



Source:

John Chenery

International Barcode of Life

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Loss Of Regulatory DNA Could Explain How Humans Developed Some Features Not Found In Other Animals

A new study demonstrates that specific traits that distinguish humans from their closest living relatives - chimpanzees, with whom we share 96 percent of our DNA - can be attributed to the loss of chunks of DNA that control when and where certain genes are turned on. The finding mirrors accumulating evidence from other species that changes to regulatory regions of DNA - rather than to the genes themselves - underlie many of the new features that organisms acquire through evolution.



Seeking specific genetic changes that might be responsible for the evolution of uniquely human traits, Howard Hughes Medical Institute investigator David Kingsley and colleagues at Stanford University scanned the human genome for features that set us apart from other mammals. The team found 510 segments that are present in chimps and other animals but missing from the human genome. Only one of the missing segments would actually disrupt a gene; the remaining 509 affect the DNA that surrounds genes, where regulatory sequences lie.



Careful analysis of a handful of these segments demonstrated that loss of regulatory DNA could explain how humans developed some features not found in other animals - such as big brains - as well as how they lost features common in other species, such as sensory whiskers and spiny penises. Their findings are published in the March 10, 2011, issue of the journal Nature.



Genes - segments of DNA that carry the blueprints for proteins - make up less than two percent of the human genome. Hidden within the remainder of our more than three billion base pairs of DNA are regulatory sequences that control when and where genes are expressed. Direct alterations to a gene can have dramatic effects, sometimes killing an organism or rendering it sterile. "In contrast, if you alter the way [a gene] turns on or off at a particular place in development, that can have a very large effect on a particular structure, but still preserve the other functions of the gene," Kingsley says. "That tends to be the sort of alternation that's favored when a new trait is evolving."



Kingsley's previous work with stickleback fish, a small spiny fish whose recent and rapid adaptation to a wide range of aquatic environments has made it ideal for evolutionary studies, have shown time and again that changes in regulatory DNA can have profound effects on an organism's traits. So when Kingsley and his colleagues searched for regions of the genome common to chimps, macaques, and mice but missing in the human genome, they weren't surprised that the sequence differences they found were almost exclusively outside of genes.



Collaborating with computational biologist Gill Bejerano's lab at Stanford, the team pinpointed 510 genetic sequences that appear in the genomes of chimps and other animals, but are "surprisingly missing" from the human genome, Kingsley says. To narrow the list so that they could focus on the changes most likely to have altered when and where particular genes were expressed, the researchers conducted a computer analysis to identify deletions that were clustered around particular genes. "We saw more changes than you would expect near genes involved in steroid hormone signaling," Kingsley says. A number of deletions also appeared near genes involved in neural development, their analysis revealed.
















But technology could only take the team so far. To zero in on specific deletions that might control human traits, the team relied on manpower: neuroscientists, physical anthropologists, developmental geneticists, and more. "We had a team of interested graduate students, postdocs, and developmental biologists poring through this list," Kingsley says. The team searched for sequences near genes known to play key roles in development, especially those known to control traits that differ between humans and other animals. "It was a fun detective hunt that led to lots of interesting discussions," he says.



The team came up with a couple dozen deletions near genes they suspected might be involved in the evolution of particular human traits. But the researchers still didn't know the normal functional roles of the missing sequences. So Kingsley and his colleagues isolated those genetic sequences from organisms that still had them (chimps or mice), attached the sequences to a reporter gene that produces a simple blue color reaction in living cells, and injected the resulting sequences into fertilized mouse eggs. By monitoring the blue color reaction in developing mice, they could see exactly where and when the sequence was turning on gene expression during embryonic or postnatal development. This gave them a way to link "the biology of the gene, the molecular change that had happened in humans, and the specific anatomical place where it really was expressed during normal development," Kingsley explains.



These experiments highlighted two segments of DNA that humans lack, but that appear to play a particularly important role in development of mice and other non-human mammals. The first is a segment of DNA that, in most animals, occurs near the gene that codes for the androgen receptor, which is associated with a variety of male-specific traits. "Males have beards, females don't," Kingsley says. "That's an example of an androgen receptor-dependent process." When the researchers inserted this sequence into mouse eggs, "what we got were blue sensory whiskers and blue genitalia," Kingsley says, indicating that when present, the sequence causes the androgen receptor to be produced in those regions.



Tracing the expression of the protein through development, Kingsley and his colleagues concluded that the sequence contributes to the development of sensory whiskers found on the faces of many mammals, and prickly surface spines found on the penises of mice and many non-human primates. Previous studies show that complete inactivation of the androgen receptor gene lead to defects in whiskers and failure to form penile spines. Although humans still retain the androgen receptor gene, the loss of regulatory information for expression in whiskers and spines could help explain two human-specific anatomical traits: absence of sensory whiskers and lack of spines on human penises. Loss of penile spines is one of several traits thought to be related to evolution of pair-bonding and monogamy in the human lineage.



The second segment of regulatory DNA they tested appears, in non-humans, near a gene called GADD45g. GADD45g normally reins in cell growth. In fact, Kingsley said, "if the gene is missing entirely, unchecked cell growth can cause pituitary tumors." When they injected the sequence into mouse eggs, they found the tell-tale blue color in a key growth layer of the developing brain - indicating that in most animals, the regulatory sequence that has disappeared in humans restricts brain growth.



The study describes some of the changes that have helped make humans human, but there are likely to be many more, Kingsley says. "By simply changing a single gene like GADD45g you're not going to be able to explain all of human brain evolution."



Still, he adds, the study shows that "it's now possible to begin identifying some of the particular molecular changes that contribute to the evolution of human traits." Human-specific traits include not only anatomical and physiological differences, but also differences in our susceptibility to many diseases, such as arthritis, cancer, malaria, HIV, Alzheimer's, and Parkinson's. "We think that the same sorts of lists and approaches will eventually help illuminate human disease susceptibilities as well," he says. "It's a great time to be studying not only where we came from, but also how our genetic history shapes many aspects of current human biology."



Source:

Jim Keeley


Howard Hughes Medical Institute

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