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Stem Cells in Treatment of Burns and Skin Ulcers

April 11, 2013, 1:27 pm
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Burns are injuries to tissues caused by heat, radiation, friction, electricity and chemicals. Burns injure the skin layers and they may also injure muscles and nerves. Skin ulcers are open sores with tissue destruction.

Epidermal stem cells have been used in treatment of burns and skin ulcers for decades in the basic form of skin grafts. Recent, technology has provided modern ways of treatment these two conditions.

The epidermis is the outer layer of the skin. This part of skin is unique because it constantly renews itself. Epidermis is made of keratinocytes mostly, but also of Langerhans cells, melanocytes and Merkel cells. In normal skin loss and traumatic skin loss like burns and skin ulcers epidermal stem cells are responsible for epidermal ability of regeneration.

Nowadays burns and skin ulcers are very common injuries. Despite their frequency, both of these injuries are very expensive for treatment because of slow-rates of healing and possible complications.

Epidermal Stem Cells

Epidermal stem cells are founded in basal layer of the skin. Epidermal stem cells produce mature functional supra basal keratinocytes. These cells are responsible for self-maintenance and self-renewal. If there is a need for extra basal cells they are able to divide themselves in several number of times in order to produce more mature functional keratinocytes.

Standard skin grafts

Skin grafting is skin transplantation to the open wound and it is used to provide coverage for wounded area. Skin grafts can be classified in autologous, allogeneic, xenogeneic and prosthetic skin grafts. In some classifications, we can find Isogeneic (transplatation between twins). Also, grafts can be classified by thickness in full-thickness grafts, split thickness grafts (these grafts are grafts with epidermis and part of the dermis) and composite grafts.

Current Use of Stem Cells in Burn Treatment

Epidermal cells can be modified both in vivo and ex vivo by viral and non-viral methods. In the first experiments with skin stem cells scientists tried to eliminate inherited genetic defects, but now these cells are used in wound healing therapy with genetically modified keratinocytes and growth factors.

The basic concept of burns treatment with stem cells is growing them on some scaffold, and then transfer to patients wound. Replacing of the skin grafts with stem cell cultures is main goal of this method. Faster healing rates and compatibility with recipient's immune system are big achievements of stem cell technique.

Main parts of stem cell production are somatic cells and egg cell. DNA from the somatic cell have to be evacuated from the somatic cell, and the rest of the cell can be discarded. Also, DNA of the egg cell is extracted and discarded. Then somatic DNA is inserted into an egg cell. The egg cell influences and reprograms the DNA from the somatic cell. This so-called embryonic cell can be induced to differentiate into skin keratinocyte under specific laboratory conditions and can be used for generating artificial skin. This is the way of creating unlimited amounts of graftable skin.

In mid-1970s, a technique for serial cultivation of epidermal cells, producing the 1000- to 10000-fold area of graftable epidermis was developed. This skin grafts were very sensitive to bacterial infection, and they can be placed directly on muscle or fascia. The only problem with this technique are expenses.

Skin has great regenerating potential. Epidermis has adult stem cells which are classified in groups on the basis of their regenerating power in: holoclone keratinocytes, paraclone keratinocytes and meroclone keratinocytes. Holoclone keratinocytes are the most important cells in this classification.

Holoclone keratinocytes

Holoclone keratinocytes are skin adult stem cells with biggest dividing potential (over 140 divisions). Only holoclone keratinocytes can be growth in vitro in addition of growth factors. Autologous holoclone keratinocytes can create full thickness skin and they can be used in treatment of massive burns. Holoclone keratinocytes grafted on damaged skin proliferate effectively and they promote healing of the burns. Lack of this method is that holoclone keratinocytes are not so efficient at deeper burns. Basic problem with this method is lack of dermal layer which supports keratinocytes layer. Thus, holoclone keratinocytes are grown on substrates. Substrates for this method must have collagen gels and cryopreserved dermis.

Fetal skin cells in grafts

This therapy method includes fetal skin cells from aborted fetuses. Fetal cells are very potent cells for regeneration. This tissue is used for patients with deeper burns, and it was imagined that this tissue is some kind of biological bandage. During the research, scientist have discovered that fetal tissue promotes growth of the patient's own skin.

This procedure starts with separation of fetal cells from the skin of aborted fetuses. Aborted fetuses skin cells divide in vitro. Then, the skin cells are allowed to grow on substrate of collagen. This procedure is used to get more than million 100cm2 grafts from a single biopsy.

The patches obtained in this way were used in burn treatments, and they have not shown any complications. It took 15 days to heal the wound. There were no retraction of the skin, and not a single one rejection of the patch. Patients grafted skin was considered as almost perfect. There was a question after this method success. What happened with fetal skin stem cells? This question remains unanswered, but one thing was sure- these grafts were better than true skin grafts.

Human umbilical cord blood stem cells

These cells have property to differentiate into epithelial cells in vitro under specific conditions. This property of human umbilical cord blood stem cells is also considered as possible solution for skin-grafting.

Also, hemopoietic stem cells transplanted on the burn sites can decrease healing time.


Standard skin grafts are very good solution for extensive burns, and it will be in nearly future basic and only solution in many parts of the world. However, considering advantages of skin stem cell tissue engineering, it is clear that this method will be the future of transplantation. The only disadvantages of this method are currently development and big expenses of tissue production.
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The BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies)

April 11, 2013, 5:01 pm
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The Human Genome project, begun in 1990 and completed in 2003, was a large collaboration between government scientists to sequence every DNA nucleotide in the human genome. It was launched amid a great fanfare, celebrating all the possible new information and therapies that could be invented simply by learning the sequence of nucleotides in human DNA. Indeed, many new insights have been discovered, and links between diseases and a person’s genetic code have been found. This achievement has given researchers and clinicians powerful tools to help develop more personalized approaches to medicine.

Now that intensive research studies into the genetic components of disease have begun, scientists are looking toward other large projects to help improve scientific research. One such initiative supported by President Obama, is called the Brain Research through Advancing Innovative Neurotechnologies Initiative (BRAIN Initiative), announced on April 2nd, has been developed to map out neurons within the brain and study how the brain functions. This information may help find information regarding the causes of a variety of neurological disorders, including schizophrenia, Alzheimer’s disease, autism, and Parkinson’s disease. The BRAIN initiative will also examine how the brain works to process memories, and possibly lead to improved treatments for neuropyschiatric disorders.

Government spending on the BRAIN Initiative is suspected to be well below that used for the Human Genome Project. The initiative has a proposed budget of only $110 million dollars, which is less than 3% of the $3.8 billion dollars spent on the Human Genome Project. Private organizations will be supplying most of the money needed for the BRAIN Initiative. Of course, though, there are arguments regarding the amount of money being spent on scientific research in general, and in particular on one initiative. However, funding into scientific researcher is essential to the nation. It provides many jobs, to professors, post-docs, students, and technicians. Scientific research also helps the nation remain competitive globally by fostering innovation. Many of the advancements we take for granted in our society are the result of government-funded research.

While the BRAIN Initiative is an exciting announcement, especially as mental health and treatment for neurological disorders become increasingly important to our society, it does raise a host of ethical considerations, just as the Human Genome Project before it. In addition to the most pressing concerns of how the studies will be conducted, who will conduct the studies, and how will research participants be protected, are questions about what will happen with the data obtained from the BRAIN Initiative.

These questions are reminiscent of those brought up by the Human Genome Project. One concern involves patents and intellectual property. Many sequences of DNA were patented during the Human Genome Project, causing worry amongst scientists that this could hamper future research. In fact, the Supreme Court is preparing to hear a case regarding patents issued on DNA sequences for several genes, including BRCA1 and BRCA2. There is a similar concern with the BRAIN Initiative that companies could patent maps of neurons within the brain. Another question raised by the completion of the Human Genome Project involved protection of individuals who have their genomes sequenced. Passage of the Genetic Nondiscrimination Act has successfully calmed fears that these individuals could be discriminated against by insurers, employers, and others based on the results of their genome sequence.

With recent events demonstrating a lack of adequate mental health care, such as shootings in Aurora, Colorado, and at Sandy Hook School, development of new insights and treatments for neuropsychiatric disorders are seen as another major benefit of the BRAIN Initiative. Funding and news releases regarding the BRAIN Initiative could spur much needed research into mental health disorders, and even prompt development of more clinical applications to be available for those suffering from mental illness. Some ethicists worry, however, that information and treatments gained from the BRAIN Initiative may be used on individuals without consent. For example, if a person is demonstrating aggressive and dangerous behavior, he or she may be forced to receive therapy that can reduce the aggression. While this would be good in one sense to protect others, it would be morally ambiguous to force someone to take medications without consent. These ethical concerns should be addressed before the BRAIN Initiative begins, in order to prevent last minute stand-offs and lengthy court proceedings.



References:
http://www.latimes.com/news/science/scie...2083.story

http://www.huffingtonpost.com/kelly-bulk...rack-obama
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Gene Therapy for Leukemia

April 12, 2013, 7:31 am
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Gene therapy is a new technique being developed with the potential to treat a variety of diseases, from genetic disorders, to infections, to cancer. Gene therapy involves inserting a new gene into a cell, either to replace a defective gene or to change a specific function of a cell. Genes are most often inserted using a virus as a vector that can deliver DNA into the cell. While gene therapy offers exciting potential treatments, it has so far not been shown to be effective or safe. Many trials of gene therapy have shown the therapy to be only marginally effective, or to actually be dangerous to the patient. For example, some children that received gene therapy to treat severe compromised immunodeficiency syndrome (SCIDS), developed leukemia as a result of the therapy.

The viral vectors used to insert genes into the cells are one major cause of the problems associated with gene therapy. Firstly, a virus, being a foreign invader, is seen by the immune system as something that needs to be attacked. This can either over-stimulate the immune system, which can inadvertently damage host cells. Secondly, the gene may not be properly inserted into the cells 100% of the time. This could cause mutations, which could subsequently cause a normal cell to develop into a cancerous cell.

Acute B cell lymphoblastic leukemia is a cancer that is typically found in children, but can also be seen in adults as an aggressive, difficult to treat cancer. Even if the cancer is successfully treated and the adult patient enters remission, acute B cell lymphoblastic leukemia has a high rate of relapse. When this occurs, the relapsed cancer is normally resistant to the chemotherapeutic drugs used previously, making the cancer more difficult to treat, and the prognosis is very bad. Recently, researchers treated 5 patients with relapsed, chemotherapy-resistant acute B cell lymphoblastic leukemia with gene therapy. In this therapy, genes were inserted into the patients’ T cells, a type of white blood cell that fights infection and cancer. The inserted genes helped the T cells more efficiently target and kill the cancerous cells. The T cells were engineered to target and attack a protein called CD19, which is found on the surface of the cancerous B cells. In addition, the T cells also received costimulatory molecules to allow them to be more easily activated in the host. The T cells were then injected back into the patients.

The gene therapy was mostly well tolerated in the patients. High levels of cytokines, proteins produced by T cells to fight infections that can be dangerous to the host in very high quantities, were found in the patients. However, this effect was short lived and easily treated with steroids, and did not stop the therapy. Researchers noted rapid decreases in tumor volume, and by the end of the treatment, the patients had no detectable cancer. After receiving the gene therapy and removing most of the cancer cells, the patients were eligible for bone marrow transplants to help completely cure the cancer. All of the patients had remission of the cancer after receiving the gene therapy. Four of the 5 patients received follow up bone marrow transplants, and three have been free of cancer for up to 24 months.

The fifth patient had a relapse of acute B cell lymphoblastic leukemia, which the researchers attributed to a lack of CD19-specific T cells. This result suggested multiple treatments with the engineered T cells could be more beneficial than single treatments. This is not an uncommon occurrence with gene therapy. Techniques to insert genes permanently into cells have not been well developed yet. In addition, cells that receive the gene may not propagate well in the host, which would require multiple treatments to maintain therapeutic efficacy. Unfortunately, repeated rounds of gene therapy are not always effective. Because the new gene is introduced using a virus, an immune response may be developed against the virus. This means that when the virus is introduced into the host again, it may be rapidly attacked and destroyed by the immune system.

While the concept of gene therapy offers hope for many, and clinical studies have given promising results, it is clear that science still has a long way to go until safe, effective gene therapy is readily available. However, data obtained from the trial described above prove that we are heading in the right direction.

References:
http://www.iol.co.za/lifestyle/gene-ther...WgAoTeRI4I
http://stm.sciencemag.org.proxy.cc.uic.e...77/177ra38
http://www.ornl.gov/sci/techresources/Hu...rapy.shtml
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Folates as possible cancer treatment - Endocyte a rising star in cancer treatment

April 12, 2013, 7:53 am
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Endocyte, a biopharmaceutical company specializing in predicative medicine and targeted drugs is designing small molecule drug conjugates intended for cancer treatment. In addition to its small molecule drug conjugates the company markets companion drugs intended as screening agents, the “companion drug imaging agent”, for the purpose of finding out what patients will be affected and to which degree by their therapies. This highly individualized approach is intended for the treatment of platinum-resistant ovarian cancer, but other targeted cancer and disease drugs are already in the pipeline research of this company.

Endocyte was formed in 1996 with a goal of designing a targeted drug delivery system discovered by Philip Low, Ph.D., at nearby Purdue University. Dr. Low, now lead researcher at Endocyte, discovered that folate can be used as a transport and delivery system for drugs, considering that most cells poses folate receptors. Folate, a B vitamin, is one of the key ingredients needed for cellular division. All cells exhibit it, but cancer cells exhibit it in a far greater quantity, considering that their division mechanism is out of control and that cancer cells multiply very rapidly. Moreover, cancer cells in particular overexpress the folate receptor and use a different pathway than healthy cells to obtain it. This specific mechanism and need for folate of cancer cells is exactly what Endocyte researchers have exploited to create a unique targeted drug conjugate which will allow selective killing of cancer cells, with minimum or no toxicity to surrounding tissues.

“This means that we can target highly potent drugs directly into cancer cells without harm to healthy cells,” says Ron Ellis, president and CEO of Endocyte.

Many potent cancer drugs have been developed and tested, and the vast majority of them have since been abandoned due to severe side effects and surrounding tissue toxicity. Endocyte used a different approach, they used an older, abandoned drug and attached it to folate, in an attempt to target cancer cells specifically and avoid damage to the surrounding tissue. The newly created drug, called vintafolide (MK-8109/EC145) is currently in phase III clinical trials for platinum resistant ovarian cancer and has so far shown to be very effective.

Vintafolide has a companion drug, etarfolatide (EC20) used to screen patients most likely to respond to treatment by vintafolide. An authorization of vintafolide and etarfolatide, for conditional approval, was obtained from the European Medicines Agency earlier this year.

The chemotherapeutic component of vintafolide is a type of vinca alkaloid absorbed exclusively by cancer cells. For the treatment of patients with platinum-resistant ovarian cancer, vintafolide is combined with pegylated liposomal doxorubicin, under the brand name Doxil. The company says that pairing up this drugs increases the chance of killing cancer cells, since using multiple drugs in combination has show effective in overcoming the cancer cells acquired immunity to therapeuticals.

“Vintafolide’s toxicity profile gives us great flexibility to combine it with other drugs,” says Ellis.
Using drugs combines in this way has been very dangerous to attempt until now, because of their cumulative toxicity.

Vintafolide has been tested in an international, multicenter Phase II trial consisting of 149 women with platinum-resistant ovarian cancer. Patients received vintafolide plus Doxil or just Doxil until either disease progression or death. The primary goal was progression-free survival. Patients taking vintafolide plus Doxil had a median progression free survival of 5 months, compared to 2.7 months for patients receiving Doxil alone.
However, in patients who tested the most positive for a specific folate receptor, the delayed progression-free survival increased from 1.5 months to 5.5, or 260%. “If you don’t have the receptor, the drug doesn’t work as well. That’s a remarkable result,” says Ellis. A Phase III trial of vintafolide in platinum-resistant ovarian cancer is under way, as well as a Phase II/III trial of vintafolide in non-small-cell lung cancer.

This approach was dubbed the “warhead” approach. Treatment for other types of cancer will consist of attaching different drugs to folate, using the specific folate metabolism of cancer cells. Other old, abandoned drugs have begun a revival with this new approach, including drugs such as platinums, microtubule destablizers, and vinca alkaloids.

“We’re designing versions that are a thousand to a million times more potent, yet less toxic,” says Ellis.

Endocyte is a rising star in the drug market, with promising stocks and even more promising research.
Location: 3000 Kent Avenue, Suite A1-100, West Lafayette, IN 47906
Phone: (765) 463-7175
Website: http://www.endocyte.com
Principals:
Ron Ellis, President and CEO
Philip Low, Ph.D., CSO
Number of Employees: 75
Focus: Endocyte develops targeted small molecule drug conjugates and companion imaging diagnostics to treat cancer and other diseases.
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Telomerase 3-D structure identified

April 12, 2013, 9:26 am
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Telomerase, a key enzyme in cells, and subsequent telomeres, have been discovered by researchers in Berkeley several years ago, leading to the 2006 Nobel Prize in medicine and physiology. Ever since its discovery, researchers have toiled to identify its complete structure and discover it’s 3-D configuration with little success. Finally, in the April 11th edition of Nature magazine, a paper has been published as the result of collaboration between researchers from UCLA and UC Berkeley, containing the complete structure of telomerase, including a 3-D model of the elusive enzyme.
"We combined every single possible method we could get our hands on to solve this structure and used cutting-edge technological advances," said co-author Jiansen Jiang, a researcher who works the study's co-senior author, Z. Hong Zhou, director of the Electron Imaging Center for Nanomachines at the California NanoSystems Institute at UCLA and a professor of microbiology, immunology and molecular genetics. "This breakthrough would not have been possible five years ago."
The culmination of decade’s worth of biochemical analysis combined with new imaging and scanning technologies has yielded in satisfying results.
"We really had to figure out how everything fit together, like a puzzle," said co-first author Edward Miracco, a National Institutes of Health postdoctoral fellow in Feigon's laboratory. "When we started fitting in the high-resolution structures to the blob that emerged from electron microscopy, we realized that everything was fitting in and made sense with decades of past biochemistry research. The project just blossomed, and the blob became a masterpiece."

Telomerase is an enzyme present in all living cells containing genes. Its function is to maintain telomeres, structures at the ends of DNA strands that serve to protect the valuable genetic material from being damaged. Telomeres act like caps at the ends of shoelaces; they keep the strands of DNA from “untangling” and being damaged by external factors. While, in all healthy cells, telomeres progressively get shorter with every division, and finally, incite cellular death when telomeres become too short to effectively protect DNA; a normal part of ageing, cancer cells work differently. More than 90% of cancer cells contain much greater amounts of telomerase, leading to their apparent “immortality” and ability to propagate almost endlessly. This new study provides tremendous value in biopharmaceutical research, allowing researchers to not only study the complex interactions of telomerase in tumorigenic cells, but also to start designing drugs that can target telomerase directly, thus shortening the life-span of tumorigenic cells significantly. Until now, designing drugs that target telomerase specifically has been like shooting in the dark, but now it is quite possible and plausible.

"Inhibiting telomerase won't hurt most healthy cells but is predicted to slow down the progression of a broad range of cancers. Our structure can be used to guide targeted drug development to inhibit telomerase, and the model system we used may also be useful to screen candidate drugs for cancer therapy."
The researchers successfully solved the structure of telomerase in Tetrahymena thermophila, a single-celled eukaryote in which telomerase and telomeres were first identified. Research on Tetrahymena telomerase in the lab of co-senior author Kathleen Collins, a professor of molecular and cell biology at UC Berkeley, laid the groundwork for the structure to be solved. "The success of this project was absolutely dependent on the collaboration among our research groups. At every step of this project, there were difficulties," Feigon said. "We had so many technical hurdles to overcome, both in the electron microscopy and biochemistry. Pretty much every problem we could have, we had, and yet at each stage these hurdles were overcome in an innovative way."
One of the biggest surprises for the researchers has been the apparent involvement of P50, a protein which acts as a hinge in telomerase, to allow movement within the complex. P50 has been shown to also play a key-role in enzymatic functions of telomerase as well as recruiting proteins to join the complex.

The beauty of this structure is that it opens up a whole new world of questions for us to answer. The exact mechanism of how this complex interacts with the telomere is an active area of future research." –Feigon finally said.

Study published in April 11th Edition of Nature
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The Use of Synthetic Biology to Help Conservation Efforts

April 12, 2013, 10:30 am
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Since the first synthetic organism was announced, controversy over the man-made creation of organisms from chemicals has been met with great debate. From a simple beginning of a cell containing chemically synthesized DNA, scientists have proposed many more adventurous projects, including the production of extinct or endangered animals. Concerns regarding the potential uses of synthetic biology are brought up regularly. The reintroduction of dangerous pathogens, such as the 1918 flu virus responsible for a pandemic that killed millions, is one major concern. In addition, moral and ethical considerations about “playing God” by creating new organisms, or even reviving extinct organisms, have been raised. Indeed, we must question what right we have to create living things to suit our needs?

With ecological research showing rapid destruction of ecosystems, and many species being endangered or killed off, conservation has become an important focal point for environmental scientists. The possibility of using synthetic biology has already been proposed to revive extinct species, with some going so far as to suggest the resurrection of species such as wooly mammoths. Bringing any animal or plant back from extinction, or the brink of extinction, has the potential to be problematic. There are concerns about how the species would survive in its new environment, and what type of effect it would have on the environment and other native species.

A long-extinct species like the mammoth would probably not be adapted to live in the current environment on earth. It would not be adapted for the climate, available food sources, predators, and even man-made factors such as pollution. Even if the species was able to survive and thrive once re-introduced into the wild, it might act as an invasive species. This means that the species could harm the environment, by depleting food supplies for other animals or preventing other native plant species from growing properly. Once an invasive species has become established in an ecosystem, it can be very difficult to remove. Endangered and more recently extinct species may not thrive either, even with assistance from synthetic biology. One large problem such species might face would be limited gene pools. This would prevent further adaptations to environmental changes. It could also result in defective recessive alleles becoming over-represented in the population, thereby propagating genetic diseases in these populations. In addition, cloning of many species has been problematic, resulting in individuals being born with severe defects, if they survive through the embryonic stage. More complex animals in particular have higher chances of experiencing these defects. If scientists were able to use synthetic biology to help breed endangered species, the individuals produced may not be viable.

A more likely scenario would be using synthetic biology to preserve species on the brink of extinction, including plants and animals. Synthetic biology could also be used to help improve the health and survivability of these endangered species. Species could be genetically engineered to express specific genes that allow them to survive and reproduce in their environment more efficiently. Synthetic biology is already successfully used in ecology, although in a more mundane manner. For example, a plant hormone called auxin is involved in helping plants develop strong roots. Scientists are able to easily produce the hormone in bacteria, and have used it to help maintain the growth of grasses in areas that are experiencing droughts.

Synthetic biology in general is a very contentious area of science, and raises a great deal of ethical concerns. These concerns are also seen in the altruistic extension of synthetic biology to conservation biology. One of the first concerns involves introducing genetically modified organisms (GMOs) into the environment. GMOs are a generally deemed worrisome by many ecologists, as the environmental and health impacts are not yet fully understood. Scientists worry that GMOs may cross-breed with native plants, thus spreading pesticide-resistance genes into weeds that could harm the environment. In addition, the long term use and consumption of GMOs by humans and other animals may have unknown consequences. As it stands, a great majority (up to 95%) of corn, soy, and cotton grown in the United States are GMO. Adding more species of plants and animals to the list of GMOs could cause additional unforeseen problems to the environment, as well as to human health.

References:
http://phys.org/news/2013-04-synthetic-b...dlife.html

http://www.scienceworldreport.com/articl...anisms.htm

http://www.todayonline.com/daily-focus/s...ic-biology
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Male Infertility and Assisted Reproductive Technologies

April 13, 2013, 5:37 am
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Infertility, or sterility, represents significant problem of human reproduction. Per definition, if after one year of regular sexual intercourse, without contraceptives, there is no pregnancy, then it can be diagnosed infertility. It is considered that frequency of infertile couples in the world is around 10%-15%. It can be said that the problem of infertility has gone up slightly. Causes of infertility are numerous and various. Infertility has traditionally been thought of as a woman's problem. However, it is clear that frequency of infertility is approximately equally distributed between the sexes.

When infertility occurs, the partners are evaluated to determine the cause and best treatment choices. In the past, men with sterility had few options as a result of limited information about causes and even less information about successful treatment. But, new tests have made it possible to determine the causes of male infertility and treatments, and assisted reproductive techniques supply hope to many couples.

Treatment is conditioned by properly conducted diagnostic. In the past decade, there is done rapid progress in the diagnosis and treatment of female infertility. Medical therapy is not changed significantly, but there are improved surgical techniques, especially the introduction of microsurgery, in certain disorders significantly expanded therapeutic options, as well as their success. However, the most important effect is the introduction of methods of in vitro sperm processing and assisted reproduction in treatment of male infertility.

In treatment of male infertility, different methods of assisting reproduction can be used. Successful methods of assisted reproductive technologies are insemination into the uterus or fallopian tubes (IUI or ITI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and modification ICSI fertilization (PICSI). For serious cases of male sterility, it is necessary to use methods, such as ICSI and PICSI.

Infertility in men with reduced sperm concentration and normal motility, or normal sperm concentrations and slightly reduced mobility can be treated with IUI procedures or ITI.

Intrauterine and Intratubal Insemination (IUI and ITI)

Sperm must be taken into a sterile dish for about 2 hours before insemination. After liquefaction of ejaculate at room temperature, it must be determined number and motility of sperm. Preparation of sperm for insemination consists of removal of seminal fluid and cellular elements. This can be accomplished in two ways. One method is used to separate the sperm on certain density gradient. By centrifuging, as sediment remained moveable sperm, that must be separated and washed, until it receives 0.5 ml concentrated medium for insemination. Another method is the "swim-up" technique in which the ejaculate is diluted with medium and centrifuged. Current portion of suspension is removed, and the residue with the sperm is left in an incubator for 30 to 60 minutes. The top layer of the medium is movable sperm, the fraction separated and used for insemination.

Sperm must undergo the process of capacitation and acrosome reaction, to be ready to fertilize the egg. Capacitation is process of functional maturation of sperm cell, which includes the reorganization of the cell membrane surface, removing inhibitory factors, changes in cellular metabolism, the flow of ions and motility of sperm. Capacitation in vivo starts when sperm cells passes through the mucus of the cervix or in vitro during the processing of seeds in the medium. Changed physiological status of sperm and changes in sperm membrane prepares sperm to initiate functional acrosome reaction. Acrosome reaction occurs on the zone pellucida where the ZP3 protein is responsible for binding of sperm cell acrosome reaction and initiation. Acrosome reaction is a process that allows the dismissal acrosoms matrix which contains a number of enzymes (serine proteases acrosin, and other hydrolytic enzymes: hyaluronidase, neuraminidase, acid phosphatase and esterase), which enables sperm cell to penetrate the egg cell.

IUI or ITI is injecting isolated sperm through the catheter at the time of natural or induced ovulation in the uterus or fallopian tube.

In Vitro Fertilization (IVF)

IVF / ET (in vitro fertilization and embryo transfer) is a method of fertilization outside the body and transfer the embryo into the uterus. The first step in applying this method is the induction of folliculogenesis drugs. Events of induced menstrual cycle are monitored by ultrasound measurement of follicular diameter and daily determination of estradiol level in serum of patients. In women, the stimulation switch is happening when least two follicles are larger than 15 mm and estradiol levels in the serum increased above 1.3 nmol / l. Then, the injection of human chorionic gonadotropin is in the ovulatory dose (10 000 IU). Preparation of oocytes for fertilization, for medical assisted technology in the laboratory, begins by aspiration and isolation of follicles just before ovulation in spontaneous or stimulated cycle.

Intracytoplasmic Sperm Injection (ICSI)

If there is a question of the sperm's ability to fertilize the egg, because of either a low sperm count or poor quality of the sperm, it can be performed intra- cytoplasmic sperm injection instead of regular in vitro fertilization. With ICSI, the eggs are retrieved the same as with conventional IVF. The oocytes and the sperm are then fertilized in the laboratory. Then, a single sperm enters the egg cytoplasm.

Preparation of gametes

Oocyte must be exempt from cumulus oophorus, which for biologists represents a delicate job. For micro-fertilization must be used only mature oocytes. Sperm is obtained by ejaculation. If this is not possible, then the various procedures of biopsies are performed, usually testicular sperm aspiration (TESA) or extraction of sperm after testicular tissue biopsy (TESE). The mature egg is held with a specialized holding pipette. A really delicate, sharp needle is used to immobilize and pick up a single sperm. This needle is then carefully inserted in to the center (cytoplasm) of the egg. The eggs are checked the next morning for evidence. Three days later the resulting embryos are simply placed into uterus, just as with IVF.

PICSI

PICSI is a method of selecting the best possible sperm for fertilisation in the IVF protocol. PICSI is a modification of micromanipulation ICSI fertilization, which selects sperm according to how well they bind to the hyaluronan around an egg cell. PICSI is dish which is coated with drops of hyaluronan. Hyaluronan occurs naturally in substances that surrounds the oocyte, and participates in the process of linking the egg and sperm cell. This means that for fertilization used exclusively sperm cells which are capable of specifically binding to the egg layer. This ability has only mature sperm cell. Research shows that sperm that binds to hyaluronan has a lower probability of chromosomal abnormalities and higher DNA integrity.
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Recovery of Adult Stem Cells from Intestinal Tissue

April 13, 2013, 6:10 am
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Research involving stem cells is a very exciting field, with promises of treatments for a variety of diseases and conditions that have few or no available treatments. Genetic disorders, cancer, injury, and other diseases could all possibly gain new therapeutics based on research performed on stem cells. The isolation and use of stem cells from embryonic tissue is very contentious, as some find the process to be morally questionable. The use of induced pluripotent stem cells, which are mature adult cells that have been reprogrammed to a more stem cell like state, and adult stem cells is met with less controversy. However, it might not be possible to develop these cells into as great a variety of mature cells, and, outside of stem cells from bone marrow, they can be difficult to isolate. While bone marrow stem cells have been used for many years to help patients replenish blood cells, it is unlikely that they could be used to produce cells for other types of tissue.

Adult stem cells isolated from specific tissues could potentially be used to help treat problems in those tissues. Studies have been performed in mice showing that tissue-specific stem cells can be isolated. Research using mouse adult stem cells has provided scientists with a basic understanding of stem cell biology. This research is an important first step to evaluate the usefulness and basic development of adult stem cells. Mouse studies are also needed to learn mechanistic information about how stem cells function. Indeed, many important advancements have already been made from studies conducted with mouse stem cells.

However, there have not been as many studies performed on human stem cells. These studies would ultimately be needed in order for stem cell therapy in humans to become available. The differences between the biology of mouse stem cells and human stem cells have prevented researchers from developing therapeutics for humans. Isolated human adult stem cells are needed to help translate the information gained from mouse studies into information that can potentially be used for human therapeutics.

Recently, researchers from the University of North Carolina, were able to isolate adult stem cells from human intestinal tissue for the first time. This is important, as it will allow researchers to study human stem cells, including how they develop, how they differ from mouse stem cells, and how they can potentially be utilized for therapeutics. These tissue-specific adult stem cells could be used to treat disorders that cannot be treated by bone marrow derived stem cells. The human intestinal stem cells are already being researched as methods to treat gastrointestinal disorders such as Irritable Bowel Syndrome (IBS), or to help cancer patients whose guts have been damaged by chemotherapy.

The researchers had previously isolated intestinal adult stem cells from mice, and successfully grew the cells in culture. They obtained samples of intestinal tissue from gastric bypass surgery patients, and began by trying to determine if the same techniques used to isolate stem cells from mice would work with human tissues. In mice, the researchers found cellular markers, termed CD24 and CD44, on stem cells. These markers were the same on human stem cells, which helped speed up the isolation process. The researchers were able to tag cells from the intestinal tissue samples with fluorescently labeled antibodies against the CD24 and CD44 markers. The cells were then isolated using a fluorescence activated cell sorter, a machine which can detect the presence of specific fluorescent molecules on the surface of the cells, and separate them from other cells lacking the fluorescent molecules. Using this technique, the researchers were also able to identify populations of active stem cells and reserve stem cells. This was exceptionally important, as researchers are currently trying to determine how reserve stem cells can be called in to replace active stem cells that have been damaged.

The isolation of adult stem cells from intestinal tissue is an important step forward in the journey to treating human diseases. Adult stem cells may soon be isolated from other tissues. As more and more types of stem cells are isolated, more advancements will be made in understanding how to use the cells in therapy. This could provide novel treatments for many patients that have had few if any therapeutic options.

References:
http://in.news.yahoo.com/adult-stem-cell...22603.html
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Scientists Make Glue from Flesh-Eating Bacteria

April 13, 2013, 9:10 am
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Growing up, one of the scariest germs I remember hearing about was flesh-eating bacteria. Everything about its name is frightening. A young child, imagining a small germ eating his or her flesh, would certainly be terrified. I imagined the skin being removed from the victim, and the bacteria escaping to infect new hosts. As I grew older and learned more about bacteria, I became interested in how something so small could cause such widespread damage to something as large as a human. Necrotizing fasciitis, the scientific name for the disease caused by flesh-eating bacteria, was simultaneously disturbing and fascinating. I had a great deal of questions about bacterial infection, and this spurred my interest in biology.

One type of bacteria that causes necrotizing fasciitis in humans is Streptococcus pyogenes. S. pyogenes produces a protein called FbaB that allows it to attach to a host cell. S. pyogenes normally enters the body through a wound, such as an animal bite, scratch, burn, or even surgical incisions. After the bacterium has attached to the host cell, it can then grow and spread, killing body tissue. Skin, fat, and the tissues covering muscles can all be destroyed during the course of the disease. Symptoms generally appear rapidly after infection. The infection may cause the patient to go into shock. If untreated, necrotizing fasciitis can cause gangrene, organ failure, and in almost 25% of cases, may eventually lead to death. Quick treatment after injury and infection is important to ensure recovery.

Being able to utilize organisms for human benefit is the main goal of biotechnology. Even harmful bacteria, such as S. pyogenes, can be manipulated for human use. It is a common theme in biotechnology to use bacteria and viruses for both research and in developing treatments for disease. Human Immunodeficiency virus (HIV), the causative agent of Acquired Immunodeficiency Syndrome (AIDS) is a common vector used as a tool in research, and is also a likely candidate for introducing new genes into cells for gene therapy. The modification of ordinarily harmful organisms for use by humans is thus not a novel concept in biotechnology research.

Scientists who study S. pyogenes have discovered a way to make the bacterium beneficial to humans. The FbaB protein, which allows the bacterium to bind to the host cell, has been engineered to act as a molecular “glue”, holding molecules together. The protein was split into two fragments, a large piece and a small piece. The large piece was named “SpyCatcher” and the small piece was named “SpyTag” (Spy is an abbreviation of S. pyogenes). When the pieces are in close proximity, they form tight covalent bonds with each other. Researchers can attach SpyTag to one protein, and SpyCatcher to another protein, to help connect the two molecules together. The interaction between SpyTag and SpyCatcher is incredibly strong, making the connection between the two molecules nearly unbreakable. Besides forming stronger connections, the SpyTag and SpyCatcher system is also more versatile than other technologies used to join proteins, as SpyTag and SpyCatcher can be used to attach two proteins together at any point on the protein. This allows scientists to be able to make many different combinations and conformations of protein constructs.

The SpyTag and SpyCatcher system could potentially be used to detect interactions among molecules in the cell, and how changes in these interactions affect disease. One proposed application of this technology is the detection of circulating tumor cells. Circulating tumor cells are cells that have come off of solid tumors, and are sent via the bloodstream to different parts of the body. Researchers believe that circulating tumor cells are part of the metastasis of tumors, allowing them to colonize remote areas of the body. In fact, circulating breast cancer tumor cells have been recently linked to metastasis to the brain. Using the SpyTag and SpyCatcher system, scientists hope to be able to detect circulating tumor cells in the blood. This would help detect cancer sooner, and it could also help determine early metastasis in patients. Early treatment of the metastatic tumor could result in increased survival. Testing using SpyTag and SpyCatcher would also be less invasive than a biopsy, as only a blood sample would be required from the patient.

References:
http://www.biologynews.net/archives/2013...teria.html

http://www.independent.co.uk/news/scienc...70288.html

http://www.webmd.com/a-to-z-guides/necro...c-overview

http://cancer.gov/newscenter/cancerresea...TumorCells
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Yeast derived Anti-malaria drug to be marketed low-cost by large international Co.

April 13, 2013, 10:59 am
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Sanofi, a pharmaceutical giant and OneWorld Health, a nonprofit drug developer said on April 12th that they launched a new project, consisting of a collaboration of several multinational organizations, to ensure large-scale production of artemisinin, a chief ingredient in anti-malarial drug production, using an older synthetic biology technology developed over a decade ago by the two organizations and Amyris with its co-founder, a University of California, Berkeley, professor, Dr. Keasling.
As part of the drug development affiliate PATH, Sanofi and OneWorld Healt intend to produce additional 35 tons of semisynthetic artemisinin this year, capping with and an average of 50 to 60 tons per year starting in 2014, at Sanofi’s Garessio site in Italy.

That would provide between 80 and 150 million artemisinin-based combination therapies (ACTs), identified by the World Health Organization in 2005 as the most effective first-line treatment available for uncomplicated malaria.
"The production of semisynthetic artemisinin will help secure part of the world's supply and maintain the cost of this raw material at acceptable levels for public health authorities around the world and ultimately benefit patients," said Robert Sebbag, M.D., vp of Access to Medicines at Sanofi. "This is a pivotal milestone in the fight against malaria."
Sanofi and OneWorld Health expevt that they will be able to add to the botanical supplies of the strain of yeast derived from the sweet wormwood plant Artemisia annua, thus accounting for inconsistencies in artemisinin supply. The collaborations states that maintaining several sources of artemisinin will contribute to a lower, more stable, price, and ultimately ensure greater availability of treatment for people with malaria, especially in impoverished countries.

Bulgaria’s Huverpharma will conduct the fermentation process leading to production of the precursor, srtemisinic acid, followed by a synthetic transformation of the artemisinic acid into artemisinin via photochemistry done by Sanofi. The artemisinin is then chemically transformed into the active antimalarial drug artesunate, and finally combined with another antimalarial drug to create the antimalarial ACT—a process that the coalition says reduces the chance that the malaria parasite will develop resistance to artemisinin.

The technology utilized here was discovered by Jay D. Keasling, Ph.D., professor of chemical engineering at UC Berkeley. Dr. Keasling—now the associate director for biosciences at Lawrence Berkeley National Laboratory, and CEO of the Joint Bioenergy Institute—was the first to discover that implanting wormwood and yeast genes into bacteria made the bacteria produce a chemical that could be chemically converted to artemisinin.
In 2006, Keasling found another gene that, when inserted into yeast with the previous genes, allowed Dr. Keasling and colleagues to synthesize small amounts of artemisinic acid. Using Dr. Keasling’s advanced synthetic biology techniques, Amyris added that gene to yeast along with other plant genes derived from wormwood and other plants to increase artemisinic acid production by a factor of 15—at which point Sanofi became interested.

Dr. Keasling and colleagues founded Amyris in 2003 to commercialize the discovery—They have thus far published the sequence of genes they introduced into the yeast in nature Magazin. The paper was posted online April 10 and will appear in Nature’s April 25 print issue.

OneWorld Health helped Dr. Keasling to transfer from his UC Berkeley lab to Amyris for a scale-up, then to Sanofi for production. OneWorld’s work was funded by two grants totaling $53.3 million from the Bill & Melinda Gates Foundation for the hope of providing significant steps in battling malaria globaly.

Sanofi stated that the price of the vaccine will be kept low for developing countries through a no-profit, no-loss production model. Dr. Keasling said UC Berkeley helped make that possible by pushing for royalty-free licensing of the process to Sanofi, which agreed in return to sell artemisinin at lower cost to countries in need.
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Use of Bispecific T Cells in Cancer Therapy

April 13, 2013, 5:28 pm
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Immunotherapeutics is a fast growing area of research for cancer therapy. Unlike traditional chemotherapy given to cancer patients, which indiscriminately kills and rapidly multiplying cell, the use of immunotherapeutics allows for targeted killing of cancer cells, thus sparing healthy cells. A new therapeutic approach is being investigated that helps direct T cells to recognize and attack cancerous cells. Two types of T cells can be activated to help fight infections and cancer: CD4+ T cells, termed helper T cells, which activate other components of the immune system, and CD8+ T cells, termed cytolytic T cells, which can directly kill infected cells and cancer cells.

A company involved in developing monoclonal antibodies for treatment of cancer, New Jersey based Immunomedics, has recently released trial results showing success using a bispecific antibody to destroy cancer cells. The bispecific antibody can bind to two separate proteins: CD19, which is found on a type of white blood cell called B cells, and a portion of CD3, which is found on a separate type of white blood cell called T cells. CD19 is highly expressed on Non-Hodgkin Lymphoma cells, which are mutated, cancerous B cells. The bispecific antibody helps direct the T cells, which are immune cells involved in protecting the host from foreign invaders and cancerous cells, to CD19-expressing cancerous B cells. Once the T cells have been directed to the cancerous B cells, they can begin the process of cell mediated immunity. The T cells can lead to the direct killing of the cancer cell. Researchers at Immunomedics have shown that the bispecific antibodies are able to direct CD3-expressing T cells to kill CD19-expressing cells in vitro at very low concentrations.

The researchers then began to test the ability of the bispecific antibody to kill cancer cells in an animal model. The researchers tested to see if the bispecific antibody could function on solid tumors. Of the animals used in the study, 6 survived, with 5 of the 6 survivors being tumor free at the end of the study. After the successful animal trials of CD19 and CD3 the bispecific antibodies, researchers at Immunomedics produced three more bispecific antibodies, expressing CD3 along with three different cancer cell specific markers. Two of the three bispecific antibody complexes were able to induce T cell mediated anti-tumor activity in animal models of pancreatic cancer and human colon cancer.

The process of how the bispecific antibody can result in T cell mediated killing of cancer cells is not fully presented in the press release from Immunomedics. In order to become fully activated, T cells need to receive a variety of signals. First, antigen must be presented to a T cell that can specifically recognize and attack that antigen. Next, several costimulatory molecules on the T cell must also be activated, to tell the T cell the antigen is from a foreign invader or cancerous cell. This helps prevent the T cell from attacking normal host cells. If the costimulatory signals are not given to the T cell, it will not be able to function. Once all of the proper activation signals have been given, the T cell can then begin to perform its function. The bispecific antibody used in trials by Immunomedics contains an antibody against CD3, a molecule found on the surface of all T cells. When CD3 is bound, either by a costimulatory factor or antibody, it helps activate the T cell. This may not be sufficient, however, to properly activate the T cells to attack cancer cells, and could result in cancer-specific T cells becoming inactive.

Another potential problem that this strategy has is that the bispecific antibody would indiscriminately activate any cell expressing CD3. This would activate any T cell in the body, not just those specific for the cancer. While the bispecific antibody would help recruit T cells to cancer cells, it would not ensure that the T cell can act against the cancer cell. Because so many T cells would be activated in the body, this could also result in an excessively high level of cytokines, the proteins produced by T cells when they are trying to remove cancerous cells. In high levels, cytokines can actually be toxic to the body, causing high levels of inflammation and damage. Despite the promising pre-clinical results of the bispecific antibody system, it is important to remain cautious as work in this area progresses.

References:
http://www.nasdaq.com/article/immunomedi...Wldy0qRI4I

http://www.immunomedics.com/pdfs/news/20...122012.pdf
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Embryonic Stem Cell Study Approved

April 14, 2013, 1:15 pm
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Stem cell therapy is a promising line of treatment for many diseases, conditions, and injuries. Neurological injuries, including injuries to the spinal cord, are difficult to treat, as neurons are not easily replicated in vitro or in vivo. Embryonic stem cells are able to mature into any cell of the body, including neurons. Stem cells could therefore be particularly useful in treating spinal cord injuries, Parkinson’s disease, and other neurological defects.

Embryonic stem cell therapies have previously been tested in animals, such as rats and mice. Previously, scientists have been able to mature human embryonic stem cells into dopamine producing cells. The dopamine producing cells were then transplanted into rats in order to treat Parkinson’s disease-like symptoms. While this treatment showed efficacy in the rats, translating such advancements to humans is very difficult. Embryonic stem cells have also been injected into mice that had spinal cord injuries. The treatment allowed partially paralyzed mice to begin walking again. Animal studies are useful for determining potential clinical efficacy. However, the artificial nature of the condition being studied using animal studies may not adequately depict the conditions in a human. For treatments such as spinal cord repair, scientists still need to learn more about how neurons are able to communicate with each other in order to achieve optimum results in human patients. In addition, because most animal studies are relatively short term compared to the life of the human, it can be difficult to gauge any long term effects from embryonic stem cell treatments.

The Food and Drug Administration (FDA) has granted approval for the first clinical trial using embryonic stem cells. The trial will test safety of stem cell treatments in patients with spinal injuries. Patients in the study have suffered complete spinal cord injury, in which there is no currently available treatment to restore function below the injury. The stem cells used in the trial are among those authorized for research during the Bush-era restriction on funding embryonic stem cell research. The main purpose of the study is to determine safety. Because embryonic stem cells have not been used yet in a clinical setting, any side effects are not yet known.

Because retrieval of embryonic stem cells requires the destruction of the four to five day old embryo, the use and study of embryonic stem cells is controversial. The stem cells used in the study were obtained from embryos left over after in vitro fertilization treatments, and would have otherwise been destroyed. The stem cells retrieved from the embryo are able to develop into any type of cell in the body. As stated above, the stem cells are among lines approved for research when Bush-era federal funding restrictions on embryonic stem cell research were instated. These lines are concerning to some researchers, as they may not be considered purely human cells. Many of these cell lines were maintained using mouse-origin feeder cells. In addition, because the cells have been maintained in culture for such a long period, they may lost some of their ability to mature into varying cell types, or even accumulated unnoticed mutations. Tumor production by transferred embryonic stem cells is another concern. If the cells have indeed mutated, and are injected into a human, the mutation might cause the embryonic stem cells to replicate rapidly, thus becoming cancerous.

The study will involve a small number of patients who have been completely paralyzed due to spinal cord injury. The will receive embryonic stem cells that have been matured in vitro into a type of cell that might be able to replace the damaged nerve cells in the spinal cord. The patients will be monitored for one year after receiving the therapy to see if there has been any recovery, in addition to monitoring for side effects from the treatment. This first test of embryonic stem cells in patients is a massive step forward for future treatments using embryonic stem cells. Scientists and clinicians will begin to determine proper dosing, implantation, and be able to identify major safety concerns. While there are many concerns regarding the safety and efficacy of embryonic stem cell therapy, the promising treatments that could be developed help justify the early risk as clinical trials begin.


References:

http://www.cnn.com/2009/HEALTH/01/23/ste...index.html

http://www.cnn.com/2008/HEALTH/12/22/ste...index.html

http://www.stemcelltherapies.org/safety.htm
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Performed Rescue Dopaminergic Neurons in Monkeys

April 14, 2013, 2:54 pm
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Despite the presence of endogenous neural stem cells, it is recognized that intrinsic “self-repair” activity for the most devastating injuries is inadequate or ineffective. This poor regenerative ability, particularly in the adult central nervous system, may be because of the limited number and restricted location of native neural stem cells, and/or limitations imposed by the surrounding microenvironment, which may not be supportive or instructive for neuronal differentiation.

Stem cells expanded ex vivo in culture, and then implanted into regions needing repair, may overcome those limitations. Whether the environment may also inhibit exogenous stem cells from surviving or differentiating toward replacement cells is a possibility. However, several transplantation experiments have suggested that neurogenic cues are transiently elaborated during degenerative processes (perhaps recapitulating developmental cues), and that exogenous stem cells are able to sense, home in on, and respond appropriately to those. In other words, stem cells appear to respond in vivo to neurogenic signals, not only when they occur during development, even at later stages by certain neurodegenerative processes.

Parkinson's Disease

Parkinson's disease is a chronic disease of the central nervous system (CNS). Parkinson’s disease is a degenerative disorder characterized by a loss of mesencephalon dopamine (DA) neurons. The loss of dopamine can cause many of motor symptoms, including tremor, slowness of movement, muscle stiffness, and impaired balance... Non-motor symptoms can cause constipation, sleep disturbances, dizziness, fatigue, depression and memory problems...

As the disease progresses, situation is getting worse, and death may result from pneumonia or pulmonary embolism due to immobility. However, patients can live many years after diagnosis, which means that the condition may not necessarily cause a reduction in lifetime.

The symptoms of Parkinson's appear when about 80 per cent of dopamine neurons are lost. That usually does not occur until age of 60, although there have been cases reported in young people. Similar to other neurodegenerative disorders, Parkinson's disease usually occurs sporadically; only 10-15% of cases are inherited and they are linked to multiple genes that can be inherited among family members.

Treatment of Parkinson's Disease

Most treatments for Parkinson's disease focus on dopamine replacement therapies. The standard for treatment of Parkinson's disease is a drug called levodopa (dopamine precursor). The effect of pharmacologic treatment tends to reduce as the disease progresses, patients also become more sensitive to treatment, and they are related side effects over time. Side effects and complications of levodopa have fuelled the search for other drugs, which are less effective, but do some benefits. These drugs are dopamine agonists, and drugs that block dopamine metabolism. Other treatments are only neuroprotective in their aim. Up to now, there are still no drugs that can slow disease progression and that is why scientists are devoting considerable efforts towards developing treatment approaches based on gene therapy, and treatment by stem cells.

Stem cell research has the potential to significantly impact the development of disease. Since the Parkinson’s disease is related to loss of dopamine (one specific chemical), stem cell therapy is theoretically possible. One of the primary goals in Parkinson's disease research is to identify a stem cell population that can be grown in appropriate conditions, maintained in the laboratory and differentiated efficiently into dopaminergic neurons. That has motivated scientists to study both embryonic and adult stem cells as an alternative source of dopamine-producing neurons.

Fetal Stem Cells

Studies in animals confirmed that the transplanted neurons could grow and make functional connections which somewhat reduced the severity of symptoms. But, the results were variable, and there are ethical also as practical problems, and this is why fetal tissue is not the best long-term source of renewable cells.

Embryonic Stem Cells

Embryonic stem cells can be readily grown and differentiated into various cell types in the body. Studies in animals using embryonic stem cell transplants are very encouraging, but there are two main challenges that impede the translation of results to clinical trials. The first is risk of developing tumours, and the second is possibility that, after many years, some of the transplanted dopamine neurons may succumb to illness.

Neural Stem Cells

Neural stem cells may be the best way to avoid the problems, which can be caused by using of embryonic stem cells. The regeneration capacity of neural cells is dependent on growth hormones and other signalling molecules that help the cells growth. Therefore, the right combination of growth factors should allow stem cells to be cultivated to a point where they are committed to becoming dopamine neurons which could then implanted in the brain.

Pluripotent Stem Cells

Pluripotent stem cells are important progress for treating neurological disease such as Parkinson's disease. Pluripotent stem cells can be used to create patient-specific cells. Scientists are now making pluripotent stem cells from people with Parkinson’s disease and using them to produce neurons in the laboratory.

New Study

In a new study, researchers obtained derived dopaminergic neurons from bone marrow stem cells in monkeys. The cells were retrieved by a regular bone marrow aspiration and then treated with growth factors. Those stem cells were directed to become dopaminergic neurons. The monkeys were treated first with a chemical to induce Parkinson's disease and then they received a transplant of the new dopaminergic neurons that had been derived from their own bone marrow stem cells. This study demonstrating that monkeys which received the transplant showed significant improvement in motor defects. This study revealed that dopaminergic neurons derived from adult bone marrow stem cells can be safely used to improve motor function in Parkinson's disease in monkeys.

There are needed further researches to understand the basic science and the various strategies for testing stem cells. It is necessary multi-disciplinary approach of scientists in order to determine safe and effective protocol for transplanting stem cells into the brain. If these therapeutic strategies are successful, it will be a great improvement in the treatment of Parkinson’s disease.
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Positive Results from Multiple Myeloma Vaccine Trial

April 14, 2013, 4:03 pm
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Multiple myeloma is a cancer of the blood, which involves rapid proliferation of plasma cells. Plasma cells are a type of antibody producing immune cell found in the bone marrow. Normally, plasma cells play an important role protecting the body against foreign pathogens and cancer. However, mutations in the plasma cells can cause them to replicate uncontrollably, resulting in higher than normal numbers of plasma cells. If the cancerous plasma cells enter the blood stream, they can colonize bone marrow in another part of the body. The increased number of plasma cells results in increased and nonspecific production of antibody. This may result in increased levels of protein in the blood stream, and the excessive growth of plasma cells can cause damage to many different systems in the body, including the immune system, kidneys, and bones. Multiple myeloma may not always require treatment, particularly if the patient is not experiencing any symptoms. When treatment is indicated, standard anti-cancer therapies are used to help the patient maintain a normal quality of life.

Vaxil Biotherapeutics recently announced positive results from an early phase clinical trial of a vaccine against multiple myeloma. The study involved 15 patients who received the vaccine, called ImMucin. The patients had previously been in remission, but were experiencing relapse of the cancer. The vaccine demonstrated considerable safety in all patients. Only minor inflammation was noted at the site of the injection, and this resolved naturally within a day. In addition, all patients developed strong, measurable adaptive immune responses in response to vaccination with ImMucin.

The vaccine consists of a short peptide of approximately 20 amino acids from the MUC1 protein, which is a marker found on multiple myeloma cancer cells. Patients were also co-treated with a cytokine called Granulocyte Macrophage Colony Stimulating Factor, or GM-CSF. GM-CSF helps tell innate immune cells within the body to grow, mature, and reproduce so that they are more effective at delivering the vaccine antigen and inducing cells from the adaptive immune system to begin attacking cancer cells.

The results of the clinical trial showed that all of the patients developed anti-MUC1 immune responses from both CD4+ T cells and CD8+ T cells. In addition, more than half of the patients developed a positive B cell response, as demonstrated by the presence of anti-MUC1 antibodies. CD4+ T cells are termed helper T cells, because they direct other components of the immune system to specifically attack and kill foreign invaders and cancerous cells. CD8+ T cells are termed cytolytic T cells, because they can directly kill virus infected cells and cancer cells. B cells are another type of adaptive immune cell, which produce a type of protein called antibody to help target immune cells to foreign microbes and cancer cells.

The increased activation of and production of antibody by B cells is somewhat worrisome, as the bone marrow plasma cells effected in multiple myeloma are a type of B cell. However, the fact that the antibodies produced are specific for the MUC1 protein indicates that only B cells capable of fighting the cancer were activated by the ImMucin vaccine. The press release provided by Vaxil did not state whether the levels of nonspecific antibodies or other proteins in the blood increased after vaccination. Regardless, the strong immune response was very exciting to researchers at Vaxil, as this indicated that the vaccine was immunogenic as is, and does not require any type of personalization which is being used in other cancer vaccines.

Nine of the fifteen patients enrolled in the ImMucin trial demonstrated positive clinical responses as well. This included reduced or stabilized levels of cancer biomarkers, and reduced levels of MUC1 detectable in the serum. The reduced levels of MUC1 were particularly encouraging, as it demonstrated a specific killing of MUC1 expressing cancer cells due to the effects of the vaccine. Importantly, even though researchers detected an increased level of anti-MUC1 antibodies, which are produced by plasma B cells, there was a decrease in the number of plasma cells in the bone marrow of some of the patients. The rising interest in immunotherapeutics as treatment for cancer, such as the ImMucin vaccine, is allowing researchers and clinicians to directly target and kill cancer cells, providing maximum therapeutic efficacy with reduced side effects compared to conventional cancer chemotherapy.


References:

http://in.finance.yahoo.com/news/vaxil-r...53348.html

http://www.mayoclinic.com/health/multipl...ma/DS00415
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New therapy for leukemia shows results and captures interest of Novartis

April 15, 2013, 7:58 am
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A new therapy for acute lymphoblastic leukemia, a swift-growing cancer that kills more than 60 percent of those afflicted, is based on extracting T cells and modifying them to home in on and destroy B cells in healthy and cancerous tissue.

Lymphoblastic leukemia has show to be very hard to treat up until now, with a high death toll, this form of leukemia can often resist conventional chemotherapies. A recent small study suggests that genetically modified immune cells can not only drive the cancer into remission, but clear it out of the patients bodies completely.

The trial was done in five patients so far, testing a new “fringe” therapy for lymphoblastic leukemia, and the results published in Science Translational Medicine, end of March. The trial was a successes, forcing the cancer into submission in 4 out of 5 patients.

The novel therapy is based on extracting immune cells called T cells from a patient, genetically modify them, and then reinfuse them back. For this purpose, the T cells were engineered to express a receptor for a protein on other immune cells, known as B cells, found in healthy and cancerous tissue. The B cells were then to be destroyed by the modified T cells, and although patients can live without B cells, cancers are completely eradicated.

Once reintroduced into the patients, the tricked T cells quickly homed in on their targets and eradicated them completely. “All of our patients very rapidly cleared the tumor,” said Michel Sadelain, a researcher at the Memorial Sloan-Kettering Cancer Center in New York and an author of the study. He says that he treatment “worked much faster than we thought”.

The technique has already been tested and shown promise against chronic leukemia, but there were considerable doubts about whether it could tackle the faster-growing acute lymphoblastic leukemia, a tenacious disease that kills more than 60% of those afflicted.

Carl June, an immunologist at the University of Pennsylvania in Philadelphia and a pioneer in engineering T cells to fight cancer, stated that he is surprised that the method worked so well against such a swift-growing cancer. The next step, he says, is to move the technique into clinical centers, and out of academic research in universities, and make it more available for a broader range of patients.

“What needs to be done is to convince oncologists and cancer biologists that this new kind of immunotherapy can work,” – said Karl June.

One of the patients involved in this trial was a 58-year-old man, who had just passed a series of high dose chemotherapy. The chemotherapy showed no effect, and after suffering the side effects and pains involved in chemotherapy, the man was left with no results, in a state of despair. Over 70% of his bone marrow was already tumor tissue. So the last hope was this new therapy.

Brentjens, oncologist, also at Memorial Sloan-Kettering Cancer Center, Sadelain and their colleagues then extracted T cells from the patient and re-engineered them to express a ‘chimeric antigen receptor’, or CAR, that would target cells expressing a protein called CD19. Because CD19 is found on both healthy and cancerous B cells, the engineered T cells were unable to distinguish between the two. However, patients can live without B cells.

Two weeks after the procedure, the patient was showing considerable signs of improvement. The treatment had driven the cancer into remission — as it did for the other four patients in the trial — so he became eligible for a bone-marrow transplant, which, in fact, saved his life. A hundred days later, he is doing well, says Brentjens. Four of the five patients were well enough to receive transplants; the remaining patient relapsed and was ineligible.

Pharmaceutical firms have tended to be wary of the CAR technique, and avoid it, because it is technically challenging, must be personalized to the patient, thus presenting a low profit opportunity, and faces an untested path to regulatory approval, beginning at clinical trials, as said by Steven Rosenberg, head of the tumor immunology section at the National Cancer Institute in Bethesda, Maryland.

But this has the potential to change. Rosenberg points to a collaboration formed in August last year between June's group and the drug giant Novartis, as well as the launch of several small CAR-focused biotechnology firms. And Sadelein says that he is currently an investigator on a trial with the Dana-Farber Cancer Institute in Boston, Massachusetts, to test whether the technique can be exported to other treatment centers, and perhaps be extended to other types of cancer, among other outcomes.


Results of this study were published in Science Translational Medicine, March 30th
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Five Mental Disorders Share Several Genetic Links?

April 15, 2013, 8:25 am
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Five major mental disorders (autism, bipolar disorder, schizophrenia, major depressive disorder and attention deficit- hyperactivity are not very similar, but they share several genetic glitches that can push the brain in other direction- direction to a mental disorder. Environmental and genetic factors are very important in developing of these mental disorders. The biggest genetic research by now shows to a genetic connection. This fascinating discovery could be the key, and maybe it can reveal what causes these five major mental disorders. Also, significant process in diagnosis and treatment of these disorders could be achieved.

Autism, schizophrenia, major depressive disorder, bipolar disorder and attention deficit- hyperactivity have been regarded as separate mental disorders. However, results of the published research suggest that these mental disorders have some genetic connection. One of the lead researchers, Dr. Jordan Smoller said that these disorder, we considered as quite different, maybe don’t have sharp boundaries between themselves. Dr. Bruce Cuthbert of the National Institute on Mental Health, which supported and funded this research, said that this theory has implications for us to understand how to diagnose mental disorders with exactly the same precision that the physical illnesses are diagnosed.

Problems with Mental Disorders Diagnostic Methods

Diagnosis of mental disorders if very complicated and it is not so precise as diagnosis of physical disorders. In every physical disorder or illness doctors have various tests sensitive for specific illness. For example, some diagnostic tests are simple examination test, which is simplest, to highly sensitive methods such as PET- scan, CT- scans, specific blood and urine tests and others diagnostic methods. On the other side, there are mental disorders and problem of their diagnosis. There are no blood tests for these disorders. Doctors rely on patients behavior and symptoms, and experts set the diagnose after their agreement. This is not objective diagnostic method, and maybe this research results will help doctors to diagnose disorders more precisely. Learning the genetic basics of mental disorders is part of good diagnostic in future, and separating for example the diagnosis of schizophrenia from some other diagnoses.

Dr. Bruce Cuthbert thinks that if scientists want to treat and diagnose peoples disorders properly, they have to find out what is really going wrong biologically. He also explained that this research is promising, but that we cannot forget that these are the early stages of understanding mental disorders.

Research Procedure and Results

Few years ago, scientists from 19 countries formed the Psychiatric Genomics Consortium and in few years this consortium has analyzed genomes of more than 61,000 people. They have analyzed genome- wide single- nucleotide polymorphism (SNP) data from 33,332 people with major depression, bipolar disorder, autism, schizophrenia and attention deficit- hyperactivity and DNA from 27,888 people without any of these mental disorders. They examined cross- disorder effects of genome- wide significant loci, identified at bipolar disorder and schizophrenia. Results of this research showed genetic variations at four chromosomal positions.
Interesting discovery of this research was that two of the four aberrations were in genes which are part of a major signaling system in human brain. Thus, this information gives clue to treatment of these five diseases. This study does not implicate that genetics of these disorders are simple. Scientists say that hundreds of genes seem to be involved. It means that this discovery of gene variations can confer just a uncertain risk of mental disorder.

In previous researches, scientist have seen similarities between these mental disorders. Case of identical twins confused researches. However, one twin had schizophrenia, but the other one had bipolar disorder. This was maybe the first clue which pointed to similarity to schizophrenia and bipolar disorder. Also, researchers had tested genomes of few families with high prevalence of mental disorders. Conclusion was the same. Two relatives with same chromosomal aberrations had different mental disorders. This conclusion is very interesting, and it can explain that two obviously different psychiatric diagnoses can have same genetic predisposition. Also, this conclusion shows clearly that examined families were not exception or maybe false positive result.

Connection Between Calcium Channels and Mental Disorders

Two of these four DNA regions have unknown influence on mental disorders development and they are located in chromosomes 3p21 and 10q24 regions. The main focus is on the other two DNA regions, L- type voltage gated calcium channel subunits, CACNB2 and CACNA1C. These two loci help in control of the transfer of calcium in and out of brain cells trough voltage channels. This calcium transfer provides a normal way of communication of the neural cells in brain. One of these two loci is possible risk gene for bipolar disorder, major depressive disorder and schizophrenia.

According to this results, calcium channels could be an important process in these five psychiatric disorders. Also, calcium channels could be potential target for new psychiatric medicines. Thus, drugs that block calcium channels function, which are used in high pressure treatment, might be suitable for treatment of mental disorders as well. However, scientist warn people with these mental disorders that they should not rush with taking these drugs, because these are preliminary research results.

Interpretation of The Results

Research findings show that chromosome aberrations are associated with various mental disorders. Crucial finding is that genes responsible for regulation of calcium transport via L-type voltage gated calcium channel have clear connection with psychopathology of the mental disorders. Also, understanding these results could change the point of view in treatment of mental illness, and possibly could open the gates to effective therapies and even prevention of these severe disorders.
According to Steven McCarroll, director of genetics for the Stanley Center for Psychiatric, scientist have only discovered the tip of an iceberg, and it is very important that the scientist had found genetic variations that pointed to a specific brain signaling system.
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Future of diagnostics - Implanted diagnostic chip

April 15, 2013, 8:52 am
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Diagnostics for chronic patients as well as patients undergoing treatment are very important. Blood diagnostics however, are expensive, require time, and cause inconvenience to the patients.

For a while now, researchers have considered implants as potential future diagnostic tools, implanting chip-sized laboratories into the patients and receiving results electronically. The chip could be implanted into several places, with different diagnostic capabilities providing most, if not all, necessary test results to the doctor, without ever inconveniencing the patient and all that much faster than conventional blood diagnostics. Such chips are in development now at several sites, but they all face several complications. Some of them include the life-span of the enzymes used on the chips, immune response-rejection problems and safety issues with the result-transmitting method.

EPFL scientists have recently developed one of these implants that might enter clinical use in just a few years. This tiny chip-sized laboratory can be implanted into patients undergoing treatment that requires continual blood testing, like, for example, chemotherapy. This chip can analyze several blood-testing parameters, and then transmit them directly to the doctor’s phone, using mobile phone networks. Swiss EPFL in Lausanne has developed this chip, and now is moving to testing it in model systems. They say it provides great news for patients suffering from chronic states such as diabetes, but not only for patients, as this new approach will ease diagnostic methods and make them more available, doctors will also benefit from increased efficacy and functionality.

This implant offers a plausible alternative while non-invasive diagnostic sensor methods are in development, say the scientists at Swiss EPFL. Non-invasive sensors can potentially be used to diagnose patients without submitting them to blood and histological tests. But this approach is yet to be fully developed and begin testing, so the scientists are looking for an alternative until then.

Each of the 5 sensor's surfaces can be covered with an enzyme that allows detecting a blood metabolite or with an antibody that captures specific protein markers. The chip's sensors, only a few cubic centimeters wide, can trace blood glucose, proteins, ATP or organic acids such as lactate simultaneously, Giovanni de Micheli and Sandro Carrara announced at DATE 13, Europe's largest electronics conference.

Potentially, we could detect just about anything," explains De Micheli. "But the enzymes have a limited lifespan." For now, the enzymes studded on the surface of the chip have a life span of roughly a month and a half, more than enough for many applications.


“After the measurement, the implant emits radio waves over a safe frequency. The patch collects the data and transmits them via Bluetooth to a mobile phone, which then sends them to the doctor over the cellular network. The implant could be particularly useful in chemotherapy applications.”
The only potential worries that this causes are related to security of the results transmitted via cellular networks, and the potential for someone to exploit them.
But, the potential application of these chips is undoubtedly great. Additional to chronic patients and people undergoing chemotherapy, the doctors can use the chip to trace for specific protein markers, thus testing patient’s tolerance to different drugs and doses. The chips can also be configures to send message alerts in certain situations, thus predicting certain symptoms, and enabling doctors to treat an illness even before it has any detectable symptoms. This will greatly improve the quality of health-care, and relieve some of the costs involved in lab-work associated with blood-tests.

The team hopes to have the chip commercially available within the next 4 years.
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Rensselaer Polytechnic Institute develops a new method to kill pathogenic bacteria

April 15, 2013, 3:16 pm
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Biomimicing nano-particles may provide with a new effective food preservation technique

Engineers and researchers at Rensselaer Polytechnic Institute have been working to develop a new method to kill deadly pathogenic bacteria, including listeria, for a range of uses, dominantly the food industry. This industrial innovation presents an alternative to the use of antibiotics or chemical decontamination in food supply systems.

Using inspiration derived from Nature, the researchers successfully adhered a cell lytic enzyme to food-safe silica nanoparticles, thus creating a coating with the demonstrated ability to selectively kill listeria-dangerous foodborne bacteria that causes an estimated 500 deaths every year in the United States. The coating kills the bacteria upon contact, even at very high concentrations, within a short time span without affecting other bacteria or organisms. The lytic enzymes can also, using this method, be attached to starch nanoparticles that are commonly used in food packaging.

Listeria is a bacterial genus containing seven species. Named after the English pioneer of sterile surgery, Joseph Lister, Listeria species are Gram-positive bacilli and are typified by ''L. monocytogenes'', and they are the the causative agents of listeriosis. This infection occurs primarily in newborn infants, elderly patients, and patients who are immune-compromised.

This new method is very flexible, and by using different lytic enzymes, could be modified to create surfaces that selectively target other deadly bacteria such as anthrax, bacillus or cocii, said Jonathan Dordick, vice president for research at Rensselaer, who helped lead the study.

This research took place in the Rensselaer Center for Biotechnology and Interdisciplinary Studies and the Rensselaer Nanoscale Science and Engineering Center for the Directed Assembly of Nanostructures, and combined the efforts and skills of chemical engineers, biotechnologists and material scientists. Collaborating with Dordick were Ravi Kane, Professor of Chemical and Biological Engineering, and Linda Schadler, associate dean for academic affairs for the Rensselaer School of Engineering.

"In this study, we have identified a new strategy for selectively killing specific types of bacteria. Stable enzyme-based coatings or sprays could be used in food supply infrastructure-from picking equipment to packaging to preparation-to kill listeria before anyone has a chance to get sick from it," said Kane. "What's most exciting is that we can adapt this technology for all different kinds of harmful or deadly bacteria."

This recent study by the same team builds upon their success in 2010 of creating a coating for killing methicillin resistant Staphylococcus aureus (MRSA), the primal culprit responsible for antibiotic resistant infections. While this coating was intended for use on surgical equipment and hospital walls, the development of a listeria-killing coating had to be food-safe, which presented additional challenge.

The team found inspiration in nature; the lytic enzymes used by viruses. Phages are viruses that infect bacterial cells, and once they have inserted their DNA and reproduced, the new viroids must escape the cells to be able to spread the infection. At that point the original phage releases a cue that activates the inserted gene that synthesizes lytic enzymes, which break down the bacterial wall from within, releasing the new generation of viruses. The team used this principle to break the walls from outside.

The next task was to stabilize the listeria-killing lytic enzymes, called Ply500, so they attached them to U.S. Food and Drug Administration-approved silica nanoparticles to create an ultra-thin film. The researchers used maltose as a binding protein to attach Ply500 to conventional, edible starch nanoparticles commonly used in food packaging. Both formulations showed as effective. Within 24 hours all listeria at concentrations as high as 100,000 bacteria per milliliter were killed. This concentrations are significantly higher than normally found in food contamination situations.

Results of the study are detailed in the paper "Enzyme-based Listericidal Nanocomposites," published April 3. in the journal Scientific Reports from the Nature Publishing Group.
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Lawrence Berkeley Laboratory Field Trip

April 15, 2013, 5:26 pm
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REPORT FIELD TRIP on March 28th 2013:
LAWRENCE BERKELEY LABORATORY FIELD TRIP
Student reporter: Katherine Miller, Biotech Club, CCSF

Tuesday, April 2, 2013

Dear fellow club members,

I would like to represent all the students and staff instructors in the field trip group from the CCSF Biotech Club to thank Doctor Corie Ralston, Doctor Simon Morton, and Dr. Peter Zwart, who gave our group the opportunity to witness the fascinating giant synchrotron system, the Advanced Light Souce (ALS) at Lawrence Berkeley National Laboratory. The ALS generates forty beam-lines, each of which is used for a different application. I also want personally to thank Rebecca D’ Urso, the field trip coordinator who had thoroughly prepared the tour, leading to its success.

The group gathered at the conference room 2202 on the second floor of building 6 of Lawrence Berkeley National Laboratory. We had a thirty-minute brief introduction with short video illustration of one of the most fascinating applications of synchrotron and its beam-line system: crystallography.

Crystallography is an essential technique to image 3-D structure of proteins. To understand why it is essential to know protein 3-D structures, we need to understand what proteins are and why they are so important in biotechnology and how they relate to the pharmaceutical industry.

Proteins (their four main atoms are linked together with multiple linkage styles between carbon, hydrogen, oxygen, and nitrogen, in addition with numerous of other atoms such as sulfur, iron, zinc, copper, etc.) in biotechnology field, are the huge bio-molecule with myriad bio-functions depending on their myriad shapes. Their shapes, in 3-D structures, are too convoluted and small to photograph by the technique of regular X-ray imaging. That is why synchrotron, the high-energy magnetic field circular system, generates electron beam; then, the beam-line system is one of the end-points that take up this high energy beam to create high-fidelity-X-ray beams at the level of photon-beam that can increase the signal-to-noise level more than thousand times that of non-synchrotron X-ray sources. Once diffraction data is collected on a target protein, its structure into the level of their atoms and their linkages can be solved.

In the pharmaceutical industry, a protein found is often the target for patho-physiology cause of a disease. Researchers try to make other proteins to either activate or inactivate this protein depending on the practical reason of the treatment for that disease. For example, incretins are a group of gastrointestinal hormones to increase the body’s sensitivity to insulin (a pancreas protein) in the treatment of diabetes mellitus. Activation of incretins by creating a linkage or breaking a linkage in their structure would lead to the increased sensitivity of the body to insulin. Incretin is made into a drug for this purpose.

How to do crystallography on a protein? Dr. Ralston instructed the group to create crystals of lysozyme, a cell enzyme for cleaning up debris inside cell matrix. Once protein crystals are made, they will be frozen in liquid nitrogen and transferred to the beam-line for imaging its structure. The beam-line has robot arms that can accurately fish up the crystal hook pockets and positions it in front of the beam-line ending box right in front of the diffraction detector camera for snap-shot one by one, and then the diffraction images are transferred into the computer system where a scientist interprets the result and determines the protein structure. Multiple snap-shots of the crystals of the same protein are generated and the more accurate image is extrapolated by the computer system.

Doctor Ralston explained that Lawrence Lab takes contracts with many pharmaceutical companies for using the beam-line system for their target proteins in their new drug manufacture, and that is paid-service contract for at least a few years for one drug! Lawrence Berkeley National Laboratory, though independently operates from UC Berkeley, has some collaborative and supportive activities in academics and beam line researches with UC Berkeley to a certain extent.

The synchrotrons system is also essential for high-tech discovery in other fields; the beam line can also be used in tomography, in imaging computer chips, etc. There are four nationally-funded synchrotrons in the US, two in California, one in Chicago, one in Long Island. There are also many synchrotrons around the world; a few are built in China, Europe, etc. These are often national and government funded system; however, private smaller synchrotrons with less investment dollars can be built separately from a large-scale synchrotron which is a multi-million dollar investment. Stanford has built an even brighter X-ray source called LCLS, which stands for Linac Coherent Light source.

The tour ended half an hour later than planned because everybody was so interested in asking many questions.

Thank you again Dr. Ralston, Dr. Morton, and Dr. Zwart and all of their staffs have given us a great opportunity to learn about this fascinating technology.

FOR YOU, who love art and technology,

The Lotus
What is prettier than the Lotus in the pond?
Green leaves, white petals, inserted by yellow pistils
Yellow pistils, white petals, green leaves,
Though living in the mud, the Lotus never stinks!
(Foreign language poem translated into English by Katherine Miller, June 2011)
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Happy 10th Anniversary, Human Genome Project

April 16, 2013, 7:20 am
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Twenty three years ago, in 1990, scientists began working together on one of the largest biological research projects ever proposed. The project proposed to sequence the 3 billion nucleotides in the human genome. It was met with great hope, from discovering the causes of many human diseases, to the eventual discovery of new treatments for these diseases. The project took 13 years to complete, at a cost of approximately three billion dollars.

When the project began, scientists estimated they would find about 100,000 distinct genes in the human genome. As the project progressed, they were stunned to find humans had only about 25,000 genes. How could an organism as complex as a human being have a number of genes similar to that of a worm? The answer was alternative splicing. Splicing is a process that occurs during transcription, or the production of mRNA, in eukaryotic cells. Introns, which are noncoding regions of nucleotides, are removed, while the exons, the coding regions, are fused, or spliced, together. This forms a mature mRNA that can direct protein production. Sometimes, though, different combinations of exons may be spliced together. These different combinations of exons allow one gene to code for the production of multiple proteins.

Another surprise to scientists was how difficult it was to determine the functions of the genes that were sequenced during the human genome project. Sequencing the genome merely told scientists which of the four DNA bases was in each position in the human genome. After the genome was sequenced, scientists had to begin the process of determining what function each gene has. Some genes had already been studied, and were easily identified after the genome was sequenced. Others were, and still are, unknown. Alternative splicing patterns, which can create multiple proteins from a single gene, further complicate the determination of gene function.

In addition to sequencing the coding regions of DNA, which tell the cell how to make proteins, scientists are now interested in determining the function of noncoding, or junk, regions of DNA. These repetitive nucleotide sequences are found in every person’s genome, and make up approximately 98% of the bases. For many years, scientists believed that these noncoding sequences had no function. They were believed to be made of remnants of retroviruses that had previously integrated into the genome and had since become inactive. Transposons, pieces of DNA that can move from one location to another, are also believed to be a component of the junk DNA. In recent years, scientists have noticed that noncoding DNA may actually play a role in the cell. Some of this junk DNA may actually function as transcription factors. These are sequences of DNA that help recruit the enzymes required for transcription of DNA into mRNA. Another idea is that the junk DNA provides variation in the population, which is important for helping the human population continue to evolve. These sequences might even help explain differences between humans and other closely related animals. This may be directly linked to the transcription factors found in noncoding DNA. The timing and amount of gene expression may lead to many of the differences between humans and other mammals.

As with many scientific endeavors, the human genome project generated far more questions than answers. However, the information gained must not be undersold. In addition to learning more about how genes function, we have developed exponentially superior technology over the past ten years. While the human genome project took 13 years and cost billions of dollars, a normal human genome can be sequenced in a few days and a cost of only a few thousand dollars. The technology has become faster, more widely available, and cheaper. Individual genome sequencing is already being used to help people determine their risk for various genetically –linked disorders. Rapid and affordable genome sequencing is also helpful for researchers who want to find differences between patients afflicted with a disorder, and volunteers without the disorder. Because of the research resulting from the sequencing of the human genome, scientists have links between genes and many human disorders, including cancer, some neurodegenerative disease, and more. By studying the defects in genes that cause these disorders, researchers might be more able to develop rational treatments. Indeed, many advancements have been made in the past 10 years, and many more are sure to come in the next 10.


References:

http://news.yahoo.com/human-genome-proje...31005.html

http://www.nytimes.com/2013/04/16/scienc....html?_r=0

http://www.sciencedaily.com/releases/200...180928.htm
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