Keith Thompson Chief Executive Cell Therapy Catapult

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Regenerative Cell Therapy 7 Toquor Abbas

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Regenerative Cell Therapy Exclusive 9 Tom

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The Next Natural Step in Genetic Engineering
Studying for Genetic Engineering, when suddenly....

By: Peter Sun Rogers

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HYBRIDS, NEPHILIM, HUMAN GENETIC ENGINEERING TRANSHUMANISM
Tom Horn discusses transhumanism and trans genetic manipulation Behind closed doors scientists and corporations have breached genetic codes that separate the individuality of all animal and...

By: Icelandic Watchman

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family genetics
Made with Explain Everything.

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How Much Do Genetics Matter For Vertical Jump? | Dre Baldwin
Vote For Team #WOYG to Play for $1 Million!: http://DreAllDay.com/TBT James Harden Signature Program http://goo.gl/JjQC2o 15-Week Ultimate Athlete Program: http://goo.gl/21OV8 Kyrie Irving...

By: Dre Baldwin

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The Sims 3 - Perfect Genetics Challenge - Pt17 - Overcrowded Party
It #39;s Issac #39;s birthday and Emma decides to throw him a birthday bash but accidentally invites too many people for our little house to cope with, Chad gets ahead at work and Mercedes comes over...

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Gene Therapy with LCA
https://www.youtube.com/edit?o=U video_id=TkFgQDIqCKw.

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Stories of Gene Therapy
Biotechnology Project Created By: Dareen Sophie.

By: Biotechnology Project

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Heart chip beats towards better drug screening, personalized medicine
Video credit: Reuters.

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The Regenerative Medicine Biotrust for Storing Cells - Mayo Clinic
The Regenerative Medicine Biotrust enables the Center for Regenerative Medicine to collect, process and store cells and other biospecimens from individual patients. As a patient #39;s own cells...

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Translational Regenerative Medicine Market 2015-2025 Report
Translational Regenerative Medicine - new study showing you trends, R D progress, and predicted revenues Where is the market for regenerative medicine heading? What are the commercial ...

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the.minouette posted a photo:

This is a linocut portrait of Gregor Mendel (1822-1884), scientist and Augustinian friar who posthumously gained fame for establishing many of the rules of heredity, fundamental to modern genetics. By carefully crossbreeeding pea plants and tracing seven characterististics (plant height, pod shape and colour, seed shape and colour, and flower position and colour) he was able to deduce what are now referred to as the laws of Mendelian inheritance. He coined the terms "recessive" and "dominant" traits. Some of his findings are subtlely alluded to in the layout of the pea flowers, like a Punnett square depicting a cross between two pea plants heterozygous for purple and white blossoms. The first edition is a variable run of 8 prints, each 11" by 14" (28 cm by 35.6 cm), on ivory Japanese kozo paper with "chine-collé" white and mauve paper.

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Gregor Mendel with his pea plants

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Nichole Bushong shares her story of helping save someone elses live

J.O. PARKER joparker@registermedia.com

It was November 2013.

Nichole Bushong of Malcom received a phone call from the National Bone Marrow Donor Program.

She was a potential match for a bone marrow recipient, and the call came to ask if she would consider some initial blood tests to see if she might be a match.

Bushong, who owns Memories Maid in Grinnell, had signed on to the national registry in June 2013 after an uncles brother needed a transplant.

He ended up getting a transplant from another donor and is doing great now, recalled Bushong.

Bushong said some people on the registry wait years before receiving a call. In her case, it was just a few months.

Nichole Bushong is shown with her husband, Lucas, on their wedding day in August 2014. Bushong, along with Sam Coster, will be in Grinnell on Wednesday, April 22 to meet with local and area residents to talk about donating and signing up for the National Bone Marrow Registry. Courtesy Photo

A story of love

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Researchers at Johns Hopkins Medicine have transformed skin cells from patients with Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS), into brain cells affected by the progressive, fatal disease and deposited those human-made cells into the first public ALS cell library, enabling scientists to better study the disease.

Using a genetic engineering technique that causes adult skin cells to transform into "pluripotent" cells, otherwise known as induced pluripotent stem cells, which can take the form of many different cells found in other parts of the body, "we make brain cells out of the patient's own skin," says Jeffrey Rothstein, M.D., Ph.D., who directs the Brain Science Institute and the Robert Packard Center for ALS Research.

While the technique for creating these human-made cells has been used by other researchers, Rothstein and his colleagues are the first to use these induced pluripotent stem cells to create the largest library of brain cell lines donated voluntarily by more than 20 ALS patients whose disease was caused by various genetic mutations. "These human cellular tools will serve as a platform to understand ALS and someday discover new drugs to treat our patients," says Rothstein, senior author of a study about the work, which was recently published online in PLOS ONE.

More than 30,000 people in the U.S. are diagnosed with ALS. Men appear to be affected slightly more than women. One of every 500 deaths in men is due to ALS, says Rothstein, "so just about everyone is going to know a neighbor, friend or family member who will eventually succumb to this terrible disease."

There is no known cure for ALS and only one FDA-approved drug, riluzole, which may only add a year to a patient's life span, says Rothstein.

Since the 1990s, researchers have studied the disease and its potential treatments in mice. The mouse model looks very much like what happens in people, Rothstein says, "but after 25 years, it has not led to the development of a drug that works in our patients." A handful of drugs were effective in mice and passed phase II clinical trials, which establish a drug's safe dosage for humans, but they all failed phase III trials, which confirm a drug's effectiveness in people.

"There has to be a sea change in how we approach ALS," Rothstein says.

Because there is no ethical or simple way to obtain brain tissue from living ALS patients, Rothstein and colleagues turned to induced pluripotent stem cell production. The technique gives researchers a tool to look at diseased human brain cells, including specialized nerve cells called astroglia, which play a critical role in ALS progression. Rothstein and his team created 22 patient-specific cell lines that included some common mutations known to be associated with ALS and deposited them in a cell library, to be shared with other scientists.

The library includes cells from patients with inherited ALS, which accounts for about 10 percent of ALS cases. Rothstein and his team also have generated cells from patients with the noninherited form of the disease -- sporadic ALS, which makes up 90 to 95 percent of ALS cases. From one patient, the researchers collected a genetic variant found in both inherited and sporadic forms of the disease, and they added that variant to the library.

Many scientists around the world have already used the library, and Rothstein hopes it will grow, with researchers making deposits of their own patients' cell lines. Eventually, induced pluripotent stem cells may be used to model diseases other than ALS and to test potential drug treatments, says Rothstein, who adds: "Now we have a real model for what's wrong with my patients."

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An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration, according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that slows the progression of the disease, which is the leading cause of vision loss in people over 65.

"This is the first study to show preservation of vision after a single injection of adult-derived human cells into a rat model with age-related macular degeneration," said Shaomei Wang, MD, PhD, lead author of the study published in the journal STEM CELLS and a research scientist in the Eye Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

The stem cell injection resulted in 130 days of preserved vision in laboratory rats, which roughly equates to 16 years in humans.

Age-related macular degeneration affects upward of 15 million Americans. It occurs when the small central portion of the retina, known as the macula, deteriorates. The retina is the light-sensing nerve tissue at the back of the eye. Macular degeneration may also be caused by environmental factors, aging and a genetic predisposition.

When animal models with macular degeneration were injected with induced neural progenitor stem cells, which derive from the more commonly known induced pluripotent stem cells, healthy cells began to migrate around the retina and formed a protective layer. This protective layer prevented ongoing degeneration of the vital retinal cells responsible for vision.

Cedars-Sinai researchers in the Induced Pluripotent Stem Cell (iPSC) Core, directed by Dhruv Sareen, PhD, with support from the David and Janet Polak Foundation Stem Cell Core Laboratory, first converted adult human skin cells into powerful induced pluripotent stem cells (iPSC), which can be expanded indefinitely and then made into any cell of the human body. In this study, these induced pluripotent stem cells were then directed toward a neural progenitor cell fate, known as induced neural progenitor stem cells, or iNPCs.

"These induced neural progenitor stem cells are a novel source of adult-derived cells which should have powerful effects on slowing down vision loss associated with macular degeneration," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and contributing author to the study. "Though additional pre-clinical data is needed, our institute is close to a time when we can offer adult stem cells as a promising source for personalized therapies for this and other human diseases."

Next steps include testing the efficacy and safety of the stem cell injection in preclinical animal studies to provide information for applying for an investigational new drug. From there, clinical trials will be designed to test potential benefit in patients with later-stage age-related macular degeneration.

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The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.

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Stem cell injection may soon reverse vision loss caused by age-related macular degeneration

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LOS ANGELES (EMBARGOED UNTIL 7 A.M. EDT on APRIL 14, 2015) - An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration, according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that slows the progression of the disease, which is the leading cause of vision loss in people over 65.

"This is the first study to show preservation of vision after a single injection of adult-derived human cells into a rat model with age-related macular degeneration," said Shaomei Wang, MD, PhD, lead author of the study published in the journal STEM CELLS and a research scientist in the Eye Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

The stem cell injection resulted in 130 days of preserved vision in laboratory rats, which roughly equates to 16 years in humans.

Age-related macular degeneration affects upward of 15 million Americans. It occurs when the small central portion of the retina, known as the macula, deteriorates. The retina is the light-sensing nerve tissue at the back of the eye. Macular degeneration may also be caused by environmental factors, aging and a genetic predisposition.

When animal models with macular degeneration were injected with induced neural progenitor stem cells, which derive from the more commonly known induced pluripotent stem cells, healthy cells began to migrate around the retina and formed a protective layer. This protective layer prevented ongoing degeneration of the vital retinal cells responsible for vision.

Cedars-Sinai researchers in the Induced Pluripotent Stem Cell (iPSC) Core, directed by Dhruv Sareen, PhD, with support from the David and Janet Polak Foundation Stem Cell Core Laboratory, first converted adult human skin cells into powerful induced pluripotent stem cells (iPSC), which can be expanded indefinitely and then made into any cell of the human body. In this study, these induced pluripotent stem cells were then directed toward a neural progenitor cell fate, known as induced neural progenitor stem cells, or iNPCs.

"These induced neural progenitor stem cells are a novel source of adult-derived cells which should have powerful effects on slowing down vision loss associated with macular degeneration," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and contributing author to the study. "Though additional pre-clinical data is needed, our institute is close to a time when we can offer adult stem cells as a promising source for personalized therapies for this and other human diseases."

Next steps include testing the efficacy and safety of the stem cell injection in preclinical animal studies to provide information for applying for an investigational new drug. From there, clinical trials will be designed to test potential benefit in patients with later-stage age-related macular degeneration.

###

Additional Cedars-Sinai authors include Dhruv Sareen, PhD; Yuchun Tsai, PhD; Bin Lu, MD, PhD; Benjamin Bakondi, PhD; Sergey Girman, PhD; and Anais Sahabian, PhD.

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Newswise Florida Atlantic University, one of Floridas leading public research universities, and the internationally renowned Nansen Neuroscience Network (NNN) in Norway, a premier network of organizations dedicated to research into neuroscience in Europe, have signed a memorandum of understanding for cooperative research and education in the areas of neuroscience and brain health.

Neuroscience research holds the key to some of the greatest challenges for our healthcare systems and societies in the decades to come, said Bjarte Reve, CEO of NNN. We believe that partnerships across countries and disciplines will be vital in addressing these challenges, and we are therefore delighted that our bonds to Florida Atlantic University and their impressive network in brain health and neuroscience are now being strengthened.

Neuroscience is a strategic research and education focus at FAU, and this new collaboration will expand upon the Universitys existing relationships with other leading scientific institutions such as Max Planck Florida Institute for Neuroscience, Scripps Florida, Torrey Pines Institute for Molecular Studies, and Vaccine and Gene Therapy Institute. In early March, FAU, Max Planck and Scripps unveiled plans to transform FAUs John D. MacArthur Campus in Jupiter into a neuroscience and life science hub in Florida.

We are extremely proud to partner with Nansen Neuroscience Network to further our research and education programs in the neurosciences, said FAU President John Kelly. Many of the top neuroscience institutions in Scandinavia, including members from Kavli Institute for Systems Neuroscience who were recently awarded the Nobel Prize in Medicine for their work in identifying the brains GPS system, are members of the Nansen Neuroscience Network. We are excited to join this prestigious organization to help address the many complex issues of brain health that impact us across the globe.

As part of the cooperative agreement, FAU and NNN plan to share specialized scientific equipment, physical facilities and support services in ways that will expand and provide more cost effective research and education for both organizations. In addition, FAUs Jupiter campus is home to both Max Planck Florida and Scripps Florida. A state-of-the-art electron microscope that is housed at Max Planck Florida is found in only a handful of places in North America and provides a unique glimpse of the brains wiring. It is the only microscope in North America capable of creating a 3D map of the brains neurons.

Neuroscience is one of the fastest developing areas of medical research and requires a multi-pronged approach through the integration of different sub disciplines, spanning from gene regulation and synaptic biology to neural systems, bioinformatics, biobanks, medical imaging, psychiatry and studies of behavior.

NNN is devoted to basic and applied research in neuroscience, including brain imaging, neurological and neuropsychiatric diseases, dementia and normal brain aging. The organizations aim is to expand the network into a comprehensive national endeavour working with patient support groups, strategic initiatives, the clinical community and industry, and from this broad network build a strong and internationally recognized innovation cluster.

FAU is home to the Center for Complex Systems and Brain Sciences and has three Ph.D. programs in neuroscience. In 2012, FAU and Max Planck initiated a joint graduate program in Integrative Biology and Neuroscience (IBAN), a strong research and academic partnership utilizing faculty from both institutions. In addition, researchers at FAU are investigating various neurodegenerative diseases such as Alzheimers and Parkinsons disease as well as addiction, epilepsy, stroke, and mental illness as a risk factor for obesity, diabetes and death.

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IMAGE:Correct tight junctions between cells labeled in yellow due to the presence of the protein PARD3. view more

Researchers at Genes and Cancer group at Bellvitge Biomedical Research Institute (IDIBELL), led by Montse Sanchez-Cespedes, have identified the PARD3 gene as a tumor suppressor that is inactivated in lung cancer squamous type. The results of the study have been published in Cancer Research.

Correct polarization (orientation in space) of bronchial epithelial cells is essential for the maintenance and proper development of this tissue under normal conditions.

PARD3 gene encodes a protein that regulates cell polarization and cell junctions. When the gene is inactivated, errors occur in this cell orientation and in contact with neighboring cells. "Any change affecting this structure promotes tumor development," said the researcher Montse Sanchez-Cespedes.

Tumor invasion and metastasis

By restoring protein encoded by PARD3 levels, both, cell lines and animal models of mice, we observed that regulating de novo polarization of cells, significantly reduced the risk of metastasis.

Lung cancer

Lung cancer is one of the tumors having higher mortality rates worldwide. Only in Spain each year about 20,000 people die from this cause. The high mortality rate is mainly due to late diagnosis of the disease, when it is already in an advanced stage.

Late detection and lack of effective therapies make the probability of survival of patients with lung cancer is very low. Overall, only 10% and 15% of patients survive more than five years after detection. The origin of more than 80% of cases is the consumption of snuff. The squamous lung cancer and lung adenocarcinoma type are the two most common types of lung tumor.

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Researchers have identified two key proteins that act as genetic 'architects', creating the blueprint needed by embryos during the earliest stages of their development.

Previous work by the research team from the Walter and Eliza Hall Institute in Melbourne, Australia, showed that the protein MOZ could relay external 'messages' to the developing embryo, revealing a mechanism for how the environment could affect development in very early pregnancy.

Dr Bilal Sheikh, Associate Professor Tim Thomas, Associate Professor Anne Voss and colleagues have now discovered that MOZ and the protein BMI1 play opposing roles in giving developing embryos the set of instructions needed to ensure that body segments including the spine, nerves and blood vessels develop correctly and in the right place.

Associate Professor Voss said the study revealed that the proteins tightly regulated Hox gene expression in early embryonic development. "In very early development, when the embryo is still just a cluster of dividing cells, the embryo must become 'organised' so that the body tissues and organs develop correctly, with everything in its right place," Associate Professor Voss said.

"The embryo is organised along an 'axis' from head to tail, and a standard pattern of development is established that subdivides the body into segments, with each segment responsible for producing specific aspects of tissues and organs, including the vertebral column, spinal cord and nerves.

"We showed that the proteins MOZ and BMI1 were important for initiating activation of the Hox genes -- section by section -- providing the blueprint the developing organism needs for proper development."

Associate Professor Voss said that, though they worked together, MOZ and BMI1 played opposing roles. "We discovered that MOZ and BMI1 were important for initiating and correctly timing Hox gene expression, ensuring the genes were activated at the right time and in the right place," she said.

MOZ was responsible for activating the genes, while BMI1 prevented Hox genes being switched on prematurely, Associate Professor Voss said.

She said the research also showed that significantly reducing Hox gene expression still allowed normal development, as long as the timing and location of expression were correct.

"We found that if the Hox genes were activated too early or late, it had significant repercussions for the developing embryo, such as malformations of the spine," Associate Professor Voss said. "Interestingly, we also found that producing an 'accurate' amount of MOZ or BMI1 in developing embryos was not nearly as important for correct development as when and where Hox genes were activated."

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Scientists uncover gene 'architects' responsible for body's blueprint

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By Edd Gent

Supercomputers and genetic engineering could help boost crops' ability to convert sunlight into energy and tackle looming food shortages, according to a team of researchers.

Photosynthesis is far from its theoretical maximum efficiency, say the authors of a paper in Cell, published on 26 March. They say that supercomputing advances could allow scientists to model every stage in the process and identify bottlenecks in improving plant growth.

But the authors add that far more science spending is needed to increase yields through these sophisticated genetic manipulations, which include refining the photosynthesis process.

"Anything we discover in the lab now won't be in a farmer's field for 20 to 30 years," says lead author Stephen Long, a plant biologist at the University of Illinois at Urbana-Champaign (UIUC) in the United States. "If we discover we have a crisis then, it's already too late."

The paper says that, by 2050, the world is predicted to require 85 per cent more staple food crops than were produced in 2013. It warns that yield gains from last century's Green Revolution are stagnating as traditional approaches to genetic improvement reach biological limits.

Instead, the group says crops such as rice and wheat, which evolved the more common C3 method of photosynthesis, could be upgraded to the more efficient C4 process found in crops such as maize, sorghum and sugar cane.

This could be done by transplanting genes from C4 plants to widen the spectrum of light the receiving plants can process and improve their growth, the scientists say.

Long's lab has demonstrated in a soon-to-be-published paper that inserting genes from cyanobacteria, a type of photosynthetic bacteria, into crop plants can make photosynthesis 30 per cent more efficient. A project backed by the philanthropic Bill & Melinda Gates Foundation is now attempting to convert rice from C3 to C4

The paper identifies two steps necessary to achieve these gains. First, techniques that allow researchers to insert genes into targeted parts of the genome must be translated from microbe biotechnology into plant biotechnology. Second, existing partial computer models of crop plants must be combined into a complete simulation.

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Africa: Photosynthesis Upgrade Proposed to Raise Crop Yields

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IMAGE:The Journal of Alternative and Complementary Medicine is a monthly peer-reviewed journal published online with Open Access options and in print. The Journal provides observational, clinical, and scientific... view more

Credit: Mary Ann Liebert, Inc., publishers

New Rochelle, NY, April 14, 2015--Malaria is a critical health problem in West Africa, where traditional medicine is commonly used alongside modern healthcare practices. An herbal remedy derived from the roots of a weed, which was traditionally used to alleviate malarial symptoms, was combined with leaves and aerial portions from two other plants with antimalarial activity, formulated as a tea, and eventually licensed and sold as an antimalarial phytomedicine. The fascinating story and challenges behind the development of this plant-based treatment are presented in The Journal of Alternative and Complementary Medicine, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on The Journal of Alternative and Complementary Medicine website until May 14, 2015.

Dr. Merlin Willcox (University of Oxford, U.K.), Dr. Zphirin Dakuyo (Phytofla, Banfora, Burkina Faso), and coauthors discuss the antimalarial and pharmacological properties of the herbal medication derived from Cochlospermum planchonii (a shrubby weed known as N'Dribala), Phyllanthus amarus, and Cassia alata. The authors provide a unique historical perspective in describing the early evaluation, development, and production of this phytomedicine. They present the ongoing research and challenges in scaling up cultivation and harvesting of the plants and in production of the final product. The article also describes other traditional uses of the medication, such as to treat hepatitis.

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About the Journal

The Journal of Alternative and Complementary Medicine is a monthly peer-reviewed journal published online with Open Access options and in print. The Journal provides observational, clinical, and scientific reports and commentary intended to help healthcare professionals and scientists evaluate and integrate therapies into patient care protocols and research strategies. Complete tables of content and a sample issue may be viewed on The Journal of Alternative and Complementary Medicine website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Alternative and Complementary Therapies, Medical Acupuncture, and Journal of Medicinal Food. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Antimalarial tea -- from herbal remedy to licensed phytomedicine

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IMAGE:Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine, is an authoritative, peer-reviewed, multidisciplinary journal published 10 times per year in print and online. The Journal publishes original... view more

Credit: Mary Ann Liebert, Inc., publishers

New Rochelle, NY, April 14, 2015--Obstetricians and gynecologists have a unique opportunity to educate and encourage minority women to nurse their infants to help reduce persistent racial and ethnic disparities in breastfeeding. As part of prenatal care, ob/gyns should promote the known health benefits of breastfeeding and help identify potential barriers their minority patients may face, according to an article in Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine published by Mary Ann Liebert, Inc., publishers. The article is available free on the Breastfeeding Medicine website until May 14, 2015.

Coauthors Katherine Jones, Michael Power, PhD, John Queenan, and Jay Schulkin, PhD, from the American College of Obstetricians and Gynecologists, American University, and Georgetown University, Washington, DC, present data from a comprehensive literature review demonstrating lower rates of breastfeeding initiation and continuation for some racial and ethnic groups in the U.S. compared to White women. By understanding the cultural and social factors and the inadequacies of the healthcare system that may affect a minority woman's decision to breastfeed and her attitudes toward nursing, ob/gyns may be better able to help their patients overcome obstacles to nursing.

In the article "Racial and Ethnic Disparities in Breastfeeding," the authors provide information such as what programs and techniques can positively impact these rates and they urge ob/gyns to use these data to support breastfeeding in their clinical practices and in public policy.

"The persistent disparities cast shame on our healthcare system, a system that continues to short change that part of our population that is most in need of the benefits of breastfeeding," says Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine. "Hopefully clinicians will incorporate the information in this article into their daily activities and reverse this negative situation."

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About the Journal

Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine, is an authoritative, peer-reviewed, multidisciplinary journal published 10 times per year in print and online. The Journal publishes original scientific papers, reviews, and case studies on a broad spectrum of topics in lactation medicine. It presents evidence-based research advances and explores the immediate and long-term outcomes of breastfeeding, including the epidemiologic, physiologic, and psychological benefits of breastfeeding. Tables of content and a sample issue may be viewed on the Breastfeeding Medicine website.

About the Publisher

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Too few minority women breastfeed -- can ob/gyns change their minds?

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IMAGE:Researchers pinpointed the locations on the blood platelet receptor proteins affected by DNA variations that alter the receptor's amino acid building blocks, including those associated with the bleeding disorder Glanzmann... view more

Credit: Laboratory of Blood and Vascular Biology at The Rockefeller University/Proceedings of the National Academy of Sciences

Accumulating data, even genetic data, is easy. Understanding the meaning of those data can be more of a challenge. As genetic testing becomes increasingly popular, more and more patients and physicians are faced with tough questions: Does a particular genetic variation translate into a predisposition to an illness, or is it simply a benign rearrangement of letters with no immediate health impacts?

To try to make sense of all the genomic data being generated, researchers at Rockefeller University studied the rate and impact of mutations in two genes associated with a blood disorder. The research was published March 31 in the Proceedings of the National Academy of Sciences, and reflects a collaboration with scientists at the Icahn School of Medicine at Mount Sinai and the ThromboGenomics consortium.

Scanning genomic data from thousands of people, the scientists -- led by postdoctoral fellow Lorena Buitrago, director of research bioinformatics Yupu Liang, and Barry S. Coller, physician in chief and vice president for medical affairs at Rockefeller -- found that about 1.3 percent of the approximately 16,000 individuals analyzed carry a mutation in at least one of the two genes they studied, which encode the proteins that make up a key receptor in blood clotting. Individuals with deleterious mutations in both copies of either gene have a rare disorder of their blood platelets, the cell fragments that prevent bleeding, termed Glanzmann thrombasthenia. Roughly 10 percent of the amino acid building blocks in these proteins were affected by the discovered mutations.

The authors then used three different commonly used algorithms to try to predict the proportion of these DNA variants that are likely to have a negative impact on health by causing excess bleeding. They got a wide range of results: Depending on the algorithm and other variables, between 27 and 71 percent of mutations were predicted to be harmful, the authors report.

To test the validity of the predictions, Buitrago made three of the variants in a cell line and examined whether they affected the production or function of the receptor. Two variants that the algorithms predicted would be deleterious did, indeed, severely affect production of the receptor. For the third variant, the algorithms were split on whether it was deleterious -- in Buitrago's experiment, this variant caused a partial decrease in the production of the receptor, but did not harm its function. "In essence, the algorithms collectively got the right answer," says Buitrago.

"It was also really striking that, in such a large population, we didn't find any of the more than 100 previously reported disease-causing mutations in these two genes," says Coller. "This means the disease-causing mutations previously reported are very rare, and thus probably first appeared relatively recently -- that is, in the past several hundred years."

The results show how challenging it can be to interpret genetic data, adds Coller. "Some variants of these two genes will likely be obviously deleterious, but it may be impossible to predict whether others are deleterious," says Coller, also the David Rockefeller Professor in the Allen and Frances Adler Laboratory of Blood and Vascular Biology. "In those cases, we will need to use additional information to judge the likelihood of a mutation being deleterious, and in many cases there will be residual uncertainty," Coller says.

If individuals have only one copy of a deleterious variant, they are unlikely to notice any impact on their health because there will be enough receptors to prevent bleeding. A more serious issue arises when two carriers of a mutated gene have children: If one percent of people carry a variant and if roughly half of the variants are deleterious, approximately three out of every 100,000 babies could carry two deleterious variants from their parents. With the human population continuing to expand at an unprecedented rate and new variants entering the genome with each generation, says Coller, it will become more important over time to use the powerful new genetic tools at our disposal to advise people of their potential genetic risks.

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Blood disorder study illustrates the challenges to parsing genetic data

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