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The Arabidopsis CERK1associated kinase PBL27 connects chitin perception to MAPK activation

These authors contributed equally to this work as first authors

These authors contributed equally to this work as third authors

Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1associated kinase PBL27, providing a missing link between pathogen perception and signaling output.

Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1associated kinase PBL27, providing a missing link between pathogen perception and signaling output.

CERK1associated kinase PBL27 interacts with MAPKKK5 at the plasma membrane.

Chitin perception induces disassociation of PBL27 and MAPKKK5.

PBL27 functions as a MAPKKK kinase.

Phosphorylation of MAPKKK5 by PBL27 is enhanced upon phosphorylation of PBL27 by CERK1.

Phosphorylation of MAPKKK5 by PBL27 is required for chitininduced MAPK activation in planta.

Kenta Yamada, Koji Yamaguchi, Tomomi Shirakawa, Hirofumi Nakagami, Akira Mine, Kazuya Ishikawa, Masayuki Fujiwara, Mari Narusaka, Yoshihiro Narusaka, Kazuya Ichimura, Yuka Kobayashi, Hidenori Matsui, Yuko Nomura, Mika Nomoto, Yasuomi Tada, Yoichiro Fukao, Tamo Fukamizo, Kenichi Tsuda, Ken Shirasu, Naoto Shibuya, Tsutomu Kawasaki

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The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the iAAA protease YME1L

These authors contributed equally to this work

The membrane scaffold SLP2 anchors a large protease complex containing the rhomboid protease PARL and the iAAA protease YME1L in the inner membrane of mitochondria, termed the SPY complex. Assembly into the SPY complex modulates PARL activity toward its substrate proteins PINK1 and PGAM5.

The membrane scaffold SLP2 anchors a large protease complex containing the rhomboid protease PARL and the iAAA protease YME1L in the inner membrane of mitochondria, termed the SPY complex. Assembly into the SPY complex modulates PARL activity toward its substrate proteins PINK1 and PGAM5.

SLP2 assembles with PARL and YME1L into the SPY complex in the mitochondrial inner membrane.

Assembly into SPY complexes modulates PARLmediated processing of PINK1 and PGAM5.

SLP2 restricts OMA1mediated processing of the OPA1.

Timothy Wai, Shotaro Saita, Hendrik Nolte, Sebastian Mller, Tim Knig, Ricarda RichterDennerlein, HansGeorg Sprenger, Joaquin Madrenas, Mareike Mhlmeister, Ulrich Brandt, Marcus Krger, Thomas Langer

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Accreditation Statement

This activity (World Immunology Summit 2016) has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of PeerPoint Medical Education Institute and Conference Series, LLC. PeerPoint Medical Education Institute is accredited by the ACCME to provide continuing medical education for physicians.

Designation Statement

PeerPoint Medical Education Institute designates the live format for this educational activity for AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Conference series invites participants from all over the world to attend "6th International Conference and Exhibition on Immunology" October 24-26, 2016 Chicago, USA includes prompt keynote presentations, Oral talks, Poster presentations and Exhibitions.

Presenters can availupto 20 CME credits..

The annual International Conference on Immunology offer a unique platform for academia, Societies and Industries interested in immunology and Biomedical sciences to share the latest trends and important issues in the field. Immunology Summit-2016 brings together the Global leaders in Immunology and relevant fields to present their research at this exclusive scientific program. The Immunology Conference hosting presentations from editors of prominent refereed journals, renowned and active investigators and decision makers in the field of Immunology. Immunology Summit 2016 Organizing Committee also intended to encourage Young investigators at every career stage to submit abstracts reporting their latest scientific findings in oral and poster sessions.

Track 1:ClinicalImmunology: Current & Future Research

Immunology is the study of the immune system. The immune system is how all animals, including humans, protect themselves against diseases. The study of diseases caused by disorders of the immune system is clinical immunology. The disorders of the immune system fall into two broad categories:

Immunodeficiency, in this immune system fails to provide an adequate response.

Autoimmunity, in this immune system attacks its own host's body.

Related:Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; 2nd international conference on innate immunity, July 21-22, 2016, Germany; International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; Immunology 2016, American Association of Immunologists, Annual MeetingMay 13-17, Los Angeles, USA;USA Immunology Conferences;InternationalConference onMucosalImmunology, July 28-29, 2016, Australia;International Congress of Immunology

Track 2:Cancer and Tumor Immunobiology

The immune system is the bodys first line of defence against most diseases and unnatural invaders.Cancer Immunobiologyis a branch ofimmunologyand it studies interactions between theimmune systemandcancer cells. These cancer cells, through subtle alterations, become immortal malignant cells but are often not changed enough to elicit an immune reaction.Understanding how the immune system worksor does not workagainst cancer is a primary focus of Cancer Immunology investigators. Certain cells of the immune system, including natural killer cells, dendritic cells (DCs) and effector T cells, are capable of driving potent anti-tumour responses.

Tumor Immunobiology

The immune system can promote the elimination of tumours, but often immune responses are modulated or suppressed by the tumour microenvironment. The Tumour microenvironment is an important aspect of cancer biology that contributes to tumour initiation, tumour progression and responses to therapy. Cells and molecules of the immune system are a fundamental component of the tumour microenvironment. Importantly, therapeutic strategies can harness the immune system to specifically target tumour cells and this is particularly appealing owing to the possibility of inducing tumour-specific immunological memory, which might cause long-lasting regression and prevent relapse in cancer patients. The composition and characteristics of the tumour micro environment vary widely and are important in determining the anti-tumour immune response. Tumour cells often induce an immunosuppressive microenvironment, which favours the development of immuno suppressive populations of immune cells, such as myeloid-derived suppressor cells and regulatory T cells.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; International Conference on Tumor Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; International Conference on Cancer Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia, 2nd international congress on Neuroimmunology & therapeutics, Dec 01-03, 2016, USA; 2nd international conference on innate immunity, July 21-22, 2016, Germany;Immunology events;9th EuropeanMucosal ImmunologyMeetings, October 9 - 12 October, Scotland; international congress on immunology, august 21-26, 2016, Australia; 4th European Immunology events September 6-9, 2015, Austria

Track 3:Inflammation and Therapies

Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process. In Inflammation the body's whiteblood cellsand substances they produce protect us from infection with foreign organisms, such as bacteria and viruses. However, in some diseases, likearthritis, the body's defense system, the immune system triggers an inflammatory response when there are no foreign invaders to fight off. In these diseases, called autoimmune diseases, the body's normally protective immune system causes damage to its own tissues. The body responds as if normal tissues are infected or somehow abnormal. Inflammation involves immune cells, blood vessels, and molecular mediators. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair. signs of acute inflammation are pain, heat, redness, swelling, and loss of function

Therapies

Inflammation Therapy is a treatment for chronic disease involving a combination of lifestyle factors and medications designed to enable the immune system to fight the disease. Techniques used include heat therapy, cold therapy, electrical stimulation, traction, massage, and acupuncture. Heat increases blood flow and makes connective tissue more flexible. It temporarily decreases joint stiffness, pain, and muscle spasms. Heat also helps reduce inflammation and the buildup of fluid in tissues (edema). Heat therapy is used to treat inflammation (including various forms of arthritis), muscle spasm, and injuries such as sprains and strains. Cold therapy Applying cold may help numb tissues and relieve muscle spasms, pain due to injuries, and low back pain or inflammation that has recently developed. Cold may be applied using an ice bag, a cold pack, or fluids (such as ethyl chloride) that cool by evaporation. The therapist limits the time and amount of cold exposure to avoid damaging tissues and reducing body temperature (causing hypothermia). Cold is not applied to tissues with a reduced blood supply (for example, when the arteries are narrowed by peripheral arterial disease).

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands ; 5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 2nd International Conference on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; International Conference on Tumor Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; International Conference on Cancer Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalcongressonImmunology, August 21-26, 2016, Australia; 18th International Conference on Inflammation, Amsterdam, Netherlands, May 12 - 13, 2016; 14th Cytokines & Inflammation Conference 2526 January 2016 San Diego, United States;

Track 4:Molecular and Structural Immunology

Molecular Immunology

Molecular immunology deals with immune responses at cellular and molecular level. Molecular immunology has been evolved for better understanding of the sub-cellular immune responses for prevention and treatment of immune related disorders and immune deficient diseases. Journal of molecular immunology focuses on the invitro and invivo immunological responses of the host. Molecular Immunology focuses on the areas such as immunological disorders, invitro and invivo immunological host responses, humoral responses, immunotherapies for treatment of cancer, treatment of autoimmune diseases such as Hashimotos disease, myasthenia gravis, rheumatoid arthritis and systemic lupus erythematosus. Treatment of Immune deficiencies such as hypersensitivities, chronic granulomatous disease, diagnostic immunology research aspects, allografts, etc..

Structural Immunology

Host immune system is an important and sophisticated system, maintaining the balance of host response to "foreign" antigens and ignorance to the normal-self. To fulfill this achievement the system manipulates a cell-cell interaction through appropriate interactions between cell-surface receptors and cell-surface ligands, or cell-secreted soluble effector molecules to their ligands/receptors/counter-receptors on the cell surface, triggering further downstream signaling for response effects. T cells and NK cells are important components of the immune system for defending the infections and malignancies and maintaining the proper response against over-reaction to the host. Receptors on the surface of T cells and NK cells include a number of important protein molecules, for example, T cell receptor (TCR), co-receptor CD8 or CD4, co-stimulator CD28, CTLA4, KIR, CD94/NKG2, LILR (ILT/LIR/CD85), Ly49, and so forth.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; 2nd international conference on innate immunity, July 21-22, 2016, Germany; International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; Immunology 2016, American Association of Immunologists, Annual MeetingMay 13-17, Los Angeles, USA;9th EuropeanMucosal ImmunologyMeetings, October 9 - 12 October, Scotland;Immunology events;International Congress of Immunology

Track 5:Transplantation Immunology

Transplantation is an act of transferring cells, tissues, or organ from one site to other. Graft is implanted cell, tissue or organ. Development of the field of organ and tissue transplantation has accelerated remarkably since the human major histocompatibility complex (mhc) was discovered in 1967. Matching of donor and recipient for mhc antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include: antibodies, antigen presenting cells, helper and cytotoxic t cell subsets, immune cell surface molecules, signaling mechanisms and cytokines that they release. The development of pharmacologic and biological agents that interfere with the alloimmune response and graft rejection has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Significant numbers of successful solid organ transplants include those of the kidneys, liver, heart and lung.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2ndInternationalCongress onNeuroimmunology&Therapeutics, Dec 01-03, 2016, USA; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands ; 2nd International Conference on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;USA Immunology Conferences;International Conference on Tumor Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; International Conference on Cancer Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK; InternationalConference onMucosalImmunology, July 28-29, 2016, Australia; Immunology events

Track 6:Infectious Diseases, Emerging and Reemerging diseases: Confronting Future Outbreaks

Infectious diseasesare disorders caused by organisms such as bacteria, viruses,fungior parasites. Many organisms live in and on our bodies. They're normally harmless or even helpful, but under certain conditions, some organisms may causedisease.Someinfectious diseasescan be passed from person to person. Many infectious diseases, such asmeaslesand chickenpox, can be prevented by vaccines. Frequent and thorough hand-washing also helps protect you from infectious diseases.

There are four main kinds of germs:

Bacteria - one-celled germs that multiply quickly and may release chemicals which can make you sick

Viruses- capsules that contain genetic material, and use your own cells to multiply

Fungi - primitive plants, like mushrooms or mildew

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

InternationalConference on Pediatric Care and Pediatric Infectious Disease, August 24-25, 2016 Philadelphia, Pennsylvania, USA; 4th InternationalCongress on Bacteriology and Infectious Diseases, May 16-18, 2016 San Antonio, Texas, USA; 2ndWorld Congress on Infectious DiseasesAugust 24 - 26, 2016 Philadelphia, Pennsylvania, USA; WorldCongress on Infection Prevention and Control, November 28-29, 2016 Valencia, Spain; Internationalconference on Emerging Infectious Diseases, Aug 24-26, Atlanta, Georgia;Immunology 2016, The 25th Annual CanadianConference on HIV/AIDSResearch Winnipeg, Manitoba, Canada , May 12, 2016 - May 15, 2016;Infectious DiseasesScandinavia-Russia Cruise 1626 June 2016, Copenhagen, Denmark; Immunology 2016, American Association of Immunologists, Annual Meeting May 13-17, Los Angeles, USA, 7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands

Track 7:Autoimmune Diseases

An autoimmune disease develops when your immune system, which defends your body against disease, decides your healthy cells are foreign. As a result, your immune system attacks healthy cells. An autoimmune disorder may result in the destruction of body tissue, abnormal growth of an organ, Changes in organ function. Depending on the type, an autoimmune disease can affect one or many different types of body tissue. Areas often affected by autoimmune disorders include Blood vessels, Connective tissues, Endocrineglands such as the thyroid or pancreas, Joints Muscles, Red blood cells, Skin It can also cause abnormal organ growth and changes in organ function. There are as many as 80 types of autoimmune diseases. Many of them have similar symptoms, which makes them very difficult to diagnose. Its also possible to have more than one at the same time. Common autoimmune disorders include Addison's disease, Dermatomyositis, Graves' disease, Hashimoto's thyroiditis, Multiple sclerosis, Myasthenia gravis, Pernicious anemia, Reactive arthritis. Autoimmune diseases usually fluctuate between periods of remission (little or no symptoms) and flare-ups (worsening symptoms). Currently, treatment for autoimmune diseases focuses on relieving symptoms because there is no curative therapy.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; 2nd international conference on innate immunity, July 21-22, 2016, Germany; 2nd International Conference andExhibition on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;Immunology events; 5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; 2nd Conference on Rheumatic and Autoimmune Diseases, June 1 to 3, 2016 Nanjing, China; 18th International Autoimmune Diseases Meetings, Paris, France, September 26 - 27, 2016; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK;International Congress of Immunology

Track 8:Viral Immunology: Emerging and Re-emerging Diseases

Immunology is the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo.

Viruses are strongly immunogenic and induces 2 types of immune responses; humoral and cellular. The repertoire of specificities of T and B cells are formed by rearrangements and somatic mutations. T and B cells do not generally recognize the same epitopes present on the same virus. B cells see the free unaltered proteins in their native 3-D conformation whereas T cells usually see the Ag in a denatured form in conjunction with MHC molecules. The characteristics of the immune reaction to the same virus may differ in different individuals depending on their genetic constitutions.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

6thInternational Conference andExhibition onImmunology,Oct 24-26, 2016, USA;InternationalConference onAutoimmunity, Oct 24-26, 2016, UK;5thEuropeanImmunologyConference, July 21-23, 2016, Germany; InternationalConference onCancer ImmunologyandImmunotherapy, July 28-30, 2016, Australia;International Conference onMucosal Immunology, July 28-29, 2016, Australia; 2nd InternationalConference on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia

Track 9:Pediatric Immunology

A child suffering from allergies or other problems with his immune system is referred as pediatric immunology. Childs immune system fights against infections. If the child has allergies, their immune system wrongly reacts to things that are usually harmless. Pet dander, pollen, dust, mold spores, insect stings, food, and medications are examples of such things. This reaction may cause their body to respond with health problems such as asthma, hay fever, hives, eczema (a rash), or a very severe and unusual reaction calledanaphylaxis. Sometimes, if your childs immune system is not working right, he may suffer from frequent, severe, and/or uncommon infections. Examples of such infections are sinusitis (inflammation of one or more of the sinuses), pneumonia (infection of the lung), thrush (a fungus infection in the mouth), and abscesses (collections of pus surrounded by inflamed tissue) that keep coming back.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

International Conference on Pediatric Care and Pediatric Infectious Disease, August 24-25, 2016 Philadelphia, Pennsylvania, USA; 7th International Conference on Pediatric Nursing and Healthcare, July 11-12, 2016 Cologne, Germany; International Congress on Pediatrics, 02-05 Jun 2016, Copenhagen, Denmark; 7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14;-15, 2016 Amsterdam, Netherlands; 2nd international conference on innate immunity, July 21-22, 2016, Germany; World Summit on Pediatric , 23 - 26 Jun 2016, Porto, Portugal; International Conference on Pediatric Nursing and Healthcare, Jul 11 - 13 2016, Cologne, Germany; Immunology 2016, American Association of Immunologists, Annual Meeting May 13-17, Los Angeles, USA; Immunology events;USA Immunology Conferences

Track 10:Immunotherapy & Cancer Immunotherapy: From Basic Biology to Translational Research

Immunotherapy is treatment that uses certain parts of a persons immune system to fight diseases such as cancer. This can be done in a couple of ways:

Stimulating your own immune system to work harder or smarter to attack cancer cells Giving you immune system components, such as man-made immune system proteins

Some types of immunotherapy are also sometimes called biologic therapy or biotherapy. In the last few decades immunotherapy has become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and theyll impact how we treat cancer in the future. Immunotherapy includes treatments that work in different ways. Some boost the bodys immune system in a very general way. Others help train the immune system to attack cancer cells specifically.

Cancer immunotherapy is the use of the immune system to treat cancer. The main types of immunotherapy now being used to treat cancer include:

Monoclonal antibodies: these are man-made versions of immune system proteins. Antibodies can be very useful in treating cancer because they can be designed to attack a very specific part of a cancer cell.

Immune checkpoint inhibitors: these drugs basically take the brakes off the immune system, which helps it recognize and attack cancer cells.

Cancer vaccines: vaccines are substances put into the body to start an immune response against certain diseases. We usually think of them as being given to healthy people to help prevent infections. But some vaccines can help prevent or treat cancer.

Other, non-specific immunotherapies: these treatments boost the immune system in a general way, but this can still help the immune system attack cancer cells.

Immunotherapy drugs are now used to treat many different types of cancer. For more information about immunotherapy as a treatment for a specific cancer, please see our information on that type of cancer.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia, 2nd internationalCongress on Neuroimmunology& therapeutics, Dec 01-03, 2016, USA;International Congress of Immunology;2nd international conference on innate immunity, July 21-22, 2016, Germany;5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 9th European Mucosal Immunology meetings, October 9 - 12 October, Scotland; international congress on immunology, august 21-26, 2016, Australia; 4th European Immunology events September 6-9, 2015, Austria

Track 11:Immunology and Diabetes

Immunologyis the study of the immune system, which is responsible for protecting the body from foreign cells such as viruses, bacteria and parasites. Immune system cells called T and B lymphocytes identify and destroy these invaders. Thelymphocytesusually recognize and ignore the bodys own tissue (a condition called immunological self-tolerance), but certain autoimmune disorders trigger a malfunction in the immune response causing an attack on the bodys own cells due to a loss ofimmune tolerance.

Type 1 diabetes is anautoimmune diseasethat occurs when the immune system mistakenly attacks insulin-producing islet cells in the pancreas. This attack begins years before type 1 diabetes becomes evident, so by the time someone is diagnosed, extensive damage has already been done and the ability to produceinsulinis lost.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

InternationalConference onMucosalImmunology, July 28-29, 2016, Australia; International Conference onAllergy, March 29-30, 2016, Spain; 2ndInternationalCongress onNeuroimmunology&Therapeutics, Dec 01-03, 2016, USA;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; Asthma EventsSeptember 14-15, 2016 Amsterdam, Netherlands;2nd InternationalConference on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; Immunology events InternationalcongressonImmunology, August 21-26, 2016, Australia; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK

Track 12:Immune Tolerance

Immunological toleranceis the failure to mount animmuneresponse to an antigen. It can be: Natural or "self"tolerance. This is the failure (a good thing) to attack the body's own proteins and other antigens. If the immunesystem should respond to "self",an autoimmune diseasemay result. Natural or "self" tolerance: Induced tolerance: This is tolerance to externalantigens that has been created by deliberately manipulating theimmune system.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

InternationalConference onMucosalImmunology, July 28-29, 2016, Australia; International Conference onAllergy, March 29-30, 2016, Spain; 2ndInternationalCongress onNeuroimmunology&Therapeutics, Dec 01-03, 2016, USA;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; Asthma EventsSeptember 14-15, 2016 Amsterdam, Netherlands;2nd InternationalExhibition on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; Immunology events InternationalcongressonImmunology, August 21-26, 2016, Australia; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK

Track 13:Vaccines and Immunotherapy

Vaccine is a biological preparation that improves immunity to particular disease. It contains certain agent that not only resembles a disease causing microorganism but it also stimulates bodys immune system to recognise the foreign agents. Vaccines are dead or inactivated organisms or purified products derived from them. whole organism vaccines purified macromolecules as vaccines,recombinant vaccines, DNA vaccines. The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. The administration of vaccines is called vaccination. In order to provide best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines with additional "booster" shots often required to achieve "full immunity".

Immunotherapy is treatment that uses certain parts of a persons immune system to fight diseases such as cancer. This can be done in a couple of ways:

Stimulating your own immune system to work harder or smarter to attack cancer cells

Giving you immune system components, such as man-made immune system proteins

Some types of immunotherapy are also sometimes called biologic therapy or biotherapy. In the last few decades immunotherapy has become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and theyll impact how we treat cancer in the future. Immunotherapy includes treatments that work in different ways. Some boost the bodys immune system in a very general way. Others help train the immune system to attack cancer cells specifically. Immunotherapy works better for some types of cancer than for others. Its used by itself for some of these cancers, but for others it seems to work better when used with other types of treatment.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

10th Euro Global Summit andExpo on Vaccines & VaccinationJune 16-18, 2016 Rome, Italy; 11th Global Summit andExpo on Vaccines, Vaccination and TherapeuticsSeptember 12-14, 2016 Phoenix, Arizona, USA; 12th Asia Pacific Global Summit andExpo on Vaccines & VaccinationNovember 24-26, 2016 Melbourne, Australia;International Congress of Immunology;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK;World Vaccine CongressApril 10-12, 2017 Washington; 10thVaccine Congress4-7 September 2016, Amsterdam, The Netherlands 10thVaccine Congress, 4-7 September 2016, Amsterdam British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK; 5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany;USA Immunology Conferences

Track 14:Immunologic Techniques, Microbial Control and Therapeutics

Immunological techniques include both experimental methods to study the immune system and methods to generate or use immunological reagents as experimental tools. The most common immunological methods relate to the production and use of antibodies to detect specific proteins in biological samples. Various laboratory techniques exist that rely on the use of antibodies to visualize components of microorganisms or other cell types and to distinguish one cell or organism type from another. Immunologic techniques are used for: Quantitating and detectingantibodiesand/orantigens, Purifying immunoglobulins, lymphokines and other molecules of the immune system, Isolating antigens and other substances important in immunological processes, Labelling antigens and antibodies, Localizing antigens and/or antibodies in tissues and cells, Detecting, and fractionatingimmunocompetent cells, Assaying forcellular immunity, Documenting cell-cell interactions, Initiating immunity and unresponsiveness, Transplantingtissues, Studying items closely related to immunity such as complement,reticuloendothelial systemand others, Molecular techniques for studying immune cells and theirreceptors, Imaging of the immune system, Methods for production or their fragments ineukaryoticandprokaryotic cells.

Microbial control:

Control of microbial growth, as used here, means to inhibit or prevent growth of microorganisms. This control is achieved in two basic ways: (1) by killing microorganisms or (2) by inhibiting the growth of microorganisms. Control of growth usually involves the use of physical or chemical agents which either kill or prevent the growth of microorganisms. Agents which kill cells are called cidal agents; agents which inhibit the growth of cells (without killing them) are referred to as static agents. Thus, the term bactericidal refers to killing bacteria, and bacteriostatic refers to inhibiting the growth of bacterial cells. A bactericide kills bacteria, a fungicide kills fungi, and so on. In microbiology, sterilization refers to the complete destruction or elimination of all viable organisms in or on a substance being sterilized. There are no degrees of sterilization: an object or substance is either sterile or not. Sterilization procedures involve the use of heat, radiation or chemicals, or physical removal of cells.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd international conference on innate immunity, July 21-22, 2016, Germany; 2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands, September 14-15, 2016 Amsterdam, Netherlands;International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; Immunology 2016, American Association of Immunologists, Annual MeetingMay 13-17, Los Angeles, USA;9th EuropeanMucosal Immunology meetings, October 9 - 12 October, Scotland;

Track 15:Immunodeficiency

Immunodeficiency is a state in which theimmune system's ability to fightinfectious diseaseis compromised or entirely absent. Immunodeficiency disorders prevent your body from adequately fighting infections and diseases. An immunodeficiency disorder also makes it easier for you to catch viruses and bacterial infections in the first place. Immunodeficiency disorders are often categorized as either congenital or acquired. A congenital, or primary, disorder is one you were born with. Acquired, or secondary, disorders are disorders you get later in life. Acquired disorders are more common thancongenital disorders. Immune system includes the following organs: spleen, tonsils, bone marrow, lymph nodes. These organs make and release lymphocytes. Lymphocytes are white blood cells classified as B cells and T cells. B and T cells fight invaders called antigens. B cells release antibodies specific to the disease your body detects. T cells kill off cells that are under attack by disease. An immunodeficiency disorder disrupts your bodys ability to defend itself against these antigens. Types of immunodeficiency disorder are Primary immunodeficiency disorders & Secondary immunodeficiency disorders.

Primary immunodeficiency disorders are immune disorders you are born with. Primary disorders include:

X-linked agammaglobulinemia (XLA)

Common variable immunodeficiency (CVID)

Severe combined immunodeficiency(SCID)

Secondary disorders happen when an outside source, such as a toxic chemical or infection, attacks your body. Severe burns and radiation also can cause secondary disorders.

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Stem Cell Basics VI. | stemcells.nih.gov

By Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

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Embryonic Stem Cells | stemcells.nih.gov

By Embryonic Stem Cells

by Junying Yu* and James A. Thomson**

Human embryonic stem (ES) cells capture the imagination because they are immortal and have an almost unlimited developmental potential (Fig. 1.1: How hESCs are derived). After many months of growth in culture dishes, these remarkable cells maintain the ability to form cells ranging from muscle to nerve to bloodpotentially any cell type that makes up the body. The proliferative and developmental potential of human ES cells promises an essentially unlimited supply of specific cell types for basic research and for transplantation therapies for diseases ranging from heart disease to Parkinson's disease to leukemia. Here we discuss the origin and properties of human ES cells, their implications for basic research and human medicine, and recent research progress since August 2001, when President George W. Bush allowed federal funding of this research for the first time. A previous report discussed progress prior to June 17, 2001 (/info/scireport/.)

Figure 1.1. How Human Embryonic Stem Cells are Derived.

( 2006 Terese Winslow)

Embryonic stem cells are derived from embryos at a developmental stage before the time that implantation would normally occur in the uterus. Fertilization normally occurs in the oviduct, and during the next few days, a series of cleavage divisions occur as the embryo travels down the oviduct and into the uterus. Each of the cells (blastomeres) of these cleavage-stage embryos are undifferentiated, i.e. they do not look or act like the specialized cells of the adult, and the blastomeres are not yet committed to becoming any particular type of differentiated cell. Indeed, each of these blastomeres has the potential to give rise to any cell of the body. The first differentiation event in humans occurs at approximately five days of development, when an outer layer of cells committed to becoming part of the placenta (the trophectoderm) separates from the inner cell mass (ICM). The ICM cells have the potential to generate any cell type of the body, but after implantation, they are quickly depleted as they differentiate to other cell types with more limited developmental potential. However, if the ICM is removed from its normal embryonic environment and cultured under appropriate conditions, the ICM-derived cells can continue to proliferate and replicate themselves indefinitely and still maintain the developmental potential to form any cell type of the body (quot;pluripotencyquot;; see Fig. 1.2: Characteristics of ESCs). These pluripotent, ICM-derived cells are ES cells.

Figure 1.2.Characteristics of Embryonic Stem Cells.

( 2006 Terese Winslow)

The derivation of mouse ES cells was first reported in 1981,1,2 but it was not until 1998 that derivation of human ES cell lines was first reported.3 Why did it take such a long time to extend the mouse results to humans? Human ES cell lines are derived from embryos produced by in vitro fertilization (IVF), a process in which oocytes and sperm are placed together to allow fertilization to take place in a culture dish. Clinics use this method to treat certain types of infertility, and sometimes, during the course of these treatments, IVF embryos are produced that are no longer needed by the couples for producing children. Currently, there are nearly 400,000 IVF-produced embryos in frozen storage in the United States alone,4 most of which will be used to treat infertility, but some of which (~2.8%) are destined to be discarded. IVF-produced embryos that would otherwise have been discarded were the sources of the human ES cell lines derived prior to President Bush's policy decision of August 2001. These human ES cell lines are now currently eligible for federal funding. Although attempts to derive human ES cells were made as early as the 1980s, culture media for human embryos produced by IVF were suboptimal. Thus, it was difficult to culture single-cell fertilized embryos long enough to obtain healthy blastocysts for the derivation of ES cell lines. Also, species-specific differences between mice and humans meant that experience with mouse ES cells was not completely applicable to the derivation of human ES cells. In the 1990s, ES cell lines from two non-human primates, the rhesus monkey5 and the common marmoset,6 were derived, and these offered closer models for the derivation of human ES cells. Experience with non-human primate ES cell lines and improvements in culture medium for human IVF-produced embryos led rapidly to the derivation of human ES cell lines in 1998.3

Because ES cells can proliferate without limit and can contribute to any cell type, human ES cells offer an unprecedented access to tissues from the human body. They will support basic research on the differentiation and function of human tissues and provide material for testing that may improve the safety and efficacy of human drugs (Figure 1.3: Promise of SC Research).7,8 For example, new drugs are not generally tested on human heart cells because no human heart cell lines exist. Instead, researchers rely on animal models. Because of important species-specific differences between animal and human hearts, however, drugs that are toxic to the human heart have occasionally entered clinical trials, sometimes resulting in death. Human ES cell-derived heart cells may be extremely valuable in identifying such drugs before they are used in clinical trials, thereby accelerating the drug discovery process and leading to safer and more effective treatments.911 Such testing will not be limited to heart cells, but to any type of human cell that is difficult to obtain by other sources.

Figure 1.3: The Promise of Stem Cell Research.

( 2006 Terese Winslow)

Human ES cells also have the potential to provide an unlimited amount of tissue for transplantation therapies to treat a wide range of degenerative diseases. Some important human diseases are caused by the death or dysfunction of one or a few cell types, e.g., insulin-producing cells in diabetes or dopaminergic neurons in Parkinson's disease. The replacement of these cells could offer a lifelong treatment for these disorders. However, there are a number of challenges to develop human ES cell-based transplantation therapies, and many years of basic research will be required before such therapies can be used to treat patients. Indeed, basic research enabled by human ES cells is likely to impact human health in ways unrelated to transplantation medicine. This impact is likely to begin well before the widespread use of ES cells in transplantation and ultimately could have a more profound long-term effect on human medicine. Since August 2001, improvements in culture of human ES cells, coupled with recent insights into the nature of pluripotency, genetic manipulation of human ES cells, and differentiation, have expanded the possibilities for these unique cells.

Mouse ES cells and human ES cells were both originally derived and grown on a layer of mouse fibroblasts (called quot;feeder cellsquot;) in the presence of bovine serum. However, the factors that sustain the growth of these two cell types appear to be distinct. The addition of the cytokine, leukemia inhibitory factor (LIF), to serum-containing medium allows mouse ES cells to proliferate in the absence of feeder cells. LIF modulates mouse ES cells through the activation of STAT3 (signal transducers and activators of transcription) protein. In serum-free culture, however, LIF alone is insufficient to prevent mouse ES cells from differentiating into neural cells. Recently, Ying et al. reported that the combination of bone morphogenetic proteins (BMPs) and LIF is sufficient to support the self-renewal of mouse ES cells.12 The effects of BMPs on mouse ES cells involve induction of inhibitor of differentiation (Id) proteins, and inhibition of extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinases (MAPK).12,13 However, LIF in the presence of serum is not sufficient to promote the self-renewal of human ES cells,3 and the LIF/STAT3 pathway appears to be inactive in undifferentiated human ES cells.14,15 Also, the addition of BMPs to human ES cells in conditions that would otherwise support ES cells leads to the rapid differentiation of human ES cells.16,17

Several groups have attempted to define growth factors that sustain human ES cells and have attempted to identify culture conditions that reduce the exposure of human ES cells to non human animal products. One important growth factor, bFGF, allows the use of a serum replacement to sustain human ES cells in the presence of fibroblasts, and this medium allowed the clonal growth of human ES cells.18 A quot;feeder-freequot; human ES cell culture system has been developed, in which human ES cells are grown on a protein matrix (mouse Matrigel or Laminin) in a bFGF-containing medium that is previously quot;conditionedquot; by co-culture with fibroblasts.19 Although this culture system eliminates direct contact of human ES cells with the fibroblasts, it does not remove the potential for mouse pathogens being introduced into the culture via the fibroblasts. Several different sources of human feeder cells have been found to support the culture of human ES cells, thus removing the possibility of pathogen transfer from mice to humans.2023 However, the possibility of pathogen transfer from human to human in these culture systems still remains. More work is still needed to develop a culture system that eliminates the use of fibroblasts entirely, which would also decrease much of the variability associated with the current culture of human ES cells. Sato et al. reported that activation of the Wnt pathway by 6-bromoindirubin3'-oxime (BIO) promotes the self-renewal of ES cells in the presence of bFGF, Matrigel, and a proprietary serum replacement product.24 Amit et al. reported that bFGF, TGF, and LIF could support some human ES cell lines in the absence of feeders.25 Although there are some questions about how well these new culture conditions will work for different human ES cell lines, there is now reason to believe that defined culture conditions for human ES cells, which reduce the potential for contamination by pathogens, will soon be achieved*.

Once a set of defined culture conditions is established for the derivation and culture of human ES cells, challenges to improve the medium will still remain. For example, the cloning efficiency of human ES cellsthe ability of a single human ES cell to proliferate and become a colonyis very low (typically less than 1%) compared to that of mouse ES cells. Another difficulty is the potential for accumulation of genetic and epigenetic changes over prolonged periods of culture. For example, karyotypic changes have been observed in several human ES cell lines after prolonged culture, and the rate at which these changes dominate a culture may depend on the culture method.26,27 The status of imprinted (epigenetically modified) genes and the stability of imprinting in various culture conditions remain completely unstudied in human ES cells**. The status of imprinted genes can clearly change with culture conditions in other cell types.28,29 These changes present potential problems if human ES cells are to be used in cell replacement therapy, and optimizing medium to reduce the rate at which genetic and epigenetic changes accumulate in culture represents a long-term endeavor. The ideal human ES cell medium, then, (a) would be cost-effective and easy to use so that many more investigators can use human ES cells as a research tool; (b) would be composed entirely of defined components not of animal origin; (c) would allow cell growth at clonal densities; and (d) would minimize the rate at which genetic and epigenetic changes accumulate in culture. Such a medium will be a challenge to develop and will most likely be achieved through a series of incremental improvements over a period of years.

Among all the newly derived human ES cell lines, twelve lines have gained the most attention. In March 2004, a South Korean group reported the first derivation of a human ES cell line (SCNT-hES-1) using the technique of somatic cell nuclear transfer (SCNT). Human somatic nuclei were transferred into human oocytes (nuclear transfer), which previously had been stripped of their own genetic material, and the resultant nuclear transfer products were cultured in vitro to the blastocyst stage for ES cell derivation.30*** Because the ES cells derived through nuclear transfer contain the same genetic material as that of the nuclear donor, the intent of the procedure is that the differentiated derivatives would not be rejected by the donor's immune system if used in transplantation therapy. More recently, the same group reported the derivation of eleven more human SCNT-ES cell lines*** with markedly improved efficiency (16.8 oocytes/line vs. 242 oocytes/line in their previous report).31*** However, given the abnormalities frequently observed in cloned animals, and the costs involved, it is not clear how useful this procedure will be in clinical applications. Also, for some autoimmune diseases, such as type I diabetes, merely providing genetically-matched tissue will be insufficient to prevent immune rejection.

Additionally, new human ES cell lines were established from embryos with genetic disorders, which were detected during the practice of preimplantation genetic diagnosis (PGD). These new cell lines may provide an excellent in vitro model for studies on the effects that the genetic mutations have on cell proliferation and differentiation.32

* Editor's note: Papers published since this writing report defined culture conditions for human embryonic stem cells. See Ludwig et al., Nat. Biotech 24: 185187, 2006; and Lu et al., PNAS 103:56885693, 2006.08.14.

** Editor's note: Papers published since the time this chapter was written address this: see Maitra et al., Nature Genetics 37, 10991103, 2005; and Rugg-Gunn et al., Nature Genetics 37:585587, 2005.

*** Editor's note: Both papers referenced in 30 and 31 were later retracted: see Science 20 Jan 2006; Vol. 311. No. 5759, p. 335.

To date, more than 120 human ES cell lines have been established worldwide,33* 67 of which are included in the National Institutes of Health (NIH) Registry. As of this writing, 21 cell lines are currently available for distribution, all of which have been exposed to animal products during their derivation. Although it has been eight years since the initial derivation of human ES cells, it is an open question as to the extent that independent human ES cell lines differ from one another. At the very least, the limited number of cell lines cannot represent a reasonable sampling of the genetic diversity of different ethnic groups in the United States, and this has consequences for drug testing, as adverse reactions to drugs often reflect a complex genetic component. Once defined culture conditions are well established for human ES cells, there will be an even more compelling need to derive additional cell lines.

* Editor's note: One recent report now estimates 414 hESC lines, see Guhr et al., http://www.StemCells.com early online version for June 15, 2006: quot;Current State of Human Embryonic Stem Cell Research: An Overview of Cell Lines and their Usage in Experimental Work.quot;

The ability of ES cells to develop into all cell types of the body has fascinated scientists for years, yet remarkably little is known about factors that make one cell pluripotent and another more restricted in its developmental potential. The transcription factor Oct4 has been used as a key marker for ES cells and for the pluripotent cells of the intact embryo, and its expression must be maintained at a critical level for ES cells to remain undifferentiated.34 The Oct4 protein itself, however, is insufficient to maintain ES cells in the undifferentiated state. Recently, two groups identified another transcription factor, Nanog, that is essential for the maintenance of the undifferentiated state of mouse ES cells.35,36 The expression of Nanog decreased rapidly as mouse ES cells differentiated, and when its expression level was maintained by a constitutive promoter, mouse ES cells could remain undifferentiated and proliferate in the absence of either LIF or BMP in serum-free medium.12 Nanog is also expressed in human ES cells, though at a much lower level compared to that of Oct4, and its function in human ES cells has yet to be examined.

By comparing gene expression patterns between different ES cell lines and between ES cells and other cell types such as adult stem cells and differentiated cells, genes that are enriched in the ES cells have been identified. Using this approach, Esg-1, an uncharacterized ES cell-specific gene, was found to be exclusively associated with pluripotency in the mouse.37 Sperger et al. identified 895 genes that are expressed at significantly higher levels in human ES cells and embryonic carcinoma cell lines, the malignant counterparts to ES cells.38 Sato et al. identified a set of 918 genes enriched in undifferentiated human ES cells compared with their differentiated counterparts; many of these genes were shared by mouse ES cells.39 Another group, however, found 92 genes, including Oct4 and Nanog, enriched in six different human ES cell lines, which showed limited overlap with those in mouse ES cell lines.40 Care must be taken to interpret these data, and the considerable differences in the results may arise from the cell lines used in the experiments, methods to prepare and maintain the cells, and the specific methods used to profile gene expression.

Since establishing human ES cells in 1998, scientists have developed genetic manipulation techniques to determine the function of particular genes, to direct the differentiation of human ES cells towards specific cell types, or to tag an ES cell derivative with a certain marker gene. Several approaches have been developed to introduce genetic elements randomly into the human ES cell genome, including electroporation, transfection by lipid-based reagents, and lentiviral vectors.4144 However, homologous recombination, a method in which a specific gene inside the ES cells is modified with an artificially introduced DNA molecule, is an even more precise method of genetic engineering that can modify a gene in a defined way at a specific locus. While this technology is routinely used in mouse ES cells, it has recently been successfully developed in human ES cells (See chapter 4: Genetically Modified Stem Cells), thus opening new doors for using ES cells as vehicles for gene therapy and for creating in vitro models of human genetic disorders such as Lesch-Nyhan disease.45,46 Another method to test the function of a gene is to use RNA interference (RNAi) to decrease the expression of a gene of interest (see Figure 1.4: RNA interference). In RNAi, small pieces of double-stranded RNA (siRNA; small interfering RNA) are either chemically synthesized and introduced directly into cells, or expressed from DNA vectors. Once inside the cells, the siRNA can lead to the degradation of the messenger RNA (mRNA), which contains the exact sequence as that of the siRNA. mRNA is the product of DNA transcription and normally can be translated into proteins. RNAi can work efficiently in somatic cells, and there has been some progress in applying this technology to human ES cells.4749

Figure 1.4. How RNAi Can Be Used To Modify Stem Cells.

( 2006 Terese Winslow)

The pluripotency of ES cells suggests possible widespread uses for these cells and their derivatives. The ES cell-derived cells can potentially be used to replace or restore tissues that have been damaged by disease or injury, such as diabetes, heart attacks, Parkinson's disease or spinal cord injury. The recent developments in these particular areas are discussed in detail in other chapters, and Table 1 summarizes recent publications in the differentiation of specific cell lineages.

The differentiation of ES cells also provides model systems to study early events in human development. Because of possible harm to the resulting child, it is not ethically acceptable to experimentally manipulate the postimplantation human embryo. Therefore, most of what is known about the mechanisms of early human embryology and human development, especially in the early postimplantation period, is based on histological sections of a limited number of human embryos and on analogy to the experimental embryology of the mouse. However, human and mouse embryos differ significantly, particularly in the formation, structure, and function of the fetal membranes and placenta, and the formation of an embryonic disc instead of an egg cylinder.5052 For example, the mouse yolk sac is a well-vascularized, robust, extraembryonic organ throughout gestation that provides important nutrient exchange functions. In humans, the yolk sac also serves important early functions, including the initiation of hematopoiesis, but it becomes essentially a vestigial structure at later times or stages in gestation. Similarly, there are dramatic differences between mouse and human placentas, both in structure and function. Thus, mice can serve in a limited capacity as a model system for understanding the developmental events that support the initiation and maintenance of human pregnancy. Human ES cell lines thus provide an important new in vitro model that will improve our understanding of the differentiation of human tissues, and thus provide important insights into processes such as infertility, pregnancy loss, and birth defects.

Human ES cells are already contributing to the study of development. For example, it is now possible to direct human ES cells to differentiate efficiently to trophoblast, the outer layer of the placenta that mediates implantation and connects the conceptus to the uterus.17,53 Another use of human ES cells is for the study of germ cell development. Cells resembling both oocytes and sperm have been successfully derived from mouse ES cells in vitro.5456 Recently, human ES cells have also been observed to differentiate into cells expressing genes characteristic of germ cells.57 Thus it may also be possible to derive oocytes and sperm from human ES cells, allowing the detailed study of human gametogenesis for the first time. Moreover, human ES cell studies are not limited to early differentiation, but are increasingly being used to understand the differentiation and functions of many human tissues, including neural, cardiac, vascular, pancreatic, hepatic, and bone (see Table 1). Moreover, transplantation of ES-derived cells has offered promising results in animal models.5867

Although scientists have gained more insights into the biology of human ES cells since 2001, many key questions remain to be addressed before the full potential of these unique cells can be realized. It is surprising, for example, that mouse and human ES cells appear to be so different with respect to the molecules that mediate their self-renewal, and perhaps even in their developmental potentials. BMPs, for example, in combination with LIF, promote the self-renewal of mouse ES cells. But in conditions that would otherwise support undifferentiated proliferation, BMPs cause rapid differentiation of human ES cells. Also, human ES cells differentiate quite readily to trophoblast, whereas mouse ES cells do so poorly, if at all. One would expect that at some level, the basic molecular mechanisms that control pluripotency would be conserved, and indeed, human and mouse ES cells share the expression of many key genes. Yet we remain remarkably ignorant about the molecular mechanisms that control pluripotency, and the nature of this remarkable cellular state has become one of the central questions of developmental biology. Of course, the other great challenge will be to continue to unravel the factors that control the differentiation of human ES cells to specific lineages, so that ES cells can fulfill their tremendous promise in basic human biology, drug screening, and transplantation medicine.

We thank Lynn Schmidt, Barbara Lewis, Sangyoon Han and Deborah J. Faupel for proofreading this report.

Notes:

* Genetics and Biotechnology Building, Madison, WI 53706, Email: jyu@primate.wisc.edu.

** John D. MacArthur Professor, Department of Anatomy, University of WisconsinMadison Medical School, The Genome Center of Wisconsin, and The Wisconsin National Primate Research Center, Madison, WI 53715, Email: thomson@primate.wisc.edu.

Introduction|Table of Contents|Chapter 2

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Embryonic Stem Cells | stemcells.nih.gov

Induced Pluripotent Stem Cell Initiative | California’s …

By Induced Pluripotent Stem Cells

The Induced Pluripotent Stem Cell (iPSC) Initiative is a major effort from CIRM to create a collection of stem cells developed from thousands of individuals.

CIRM is creating the iPSC bank so that scientists can use the cells, either in a petri dish or transplanted into animals, to study how disease develops and progresses and develop and test new drugs or other therapies. The iPSC bank is now open and cell lines are available at catalog.coriell.org/CIRM.

The large size of the collection will provide researchers with a powerful tool for studying genetic variation between individuals, helping scientists understand how disease and treatment may vary in a diverse population like Californias.

Outside Stem Cell Lines

The CIRM iPSC Repository is now accepting up to 300 human pluripotent stem cell lines (including human Embryonic Stem Cells or human induced Pluripotent Stem Cells) from outside laboratories. Submitted lines can be expanded, at no cost to the investigator, for storage and distribution in the Repository.

The deadline for cell line submission is October 12, 2016. For more information about this opportunity and for submission criteria, see attached document below:

What is the iPSC Initative? How does it work? Why iPS cells? Who is generating the cells? Which diseases will be represented? How many samples are being collected for each condition?

What is the iPSC Initiative? The Human Induced Pluripotent Stem Cell (hiPSC) Initiative is one of the California stem cell agencys major efforts to provide valuable resources to the research community. The goal is to create a bank of high quality stem cell lines developed from thousands of individuals for use in research.

How does it work? Blood or skin samples collected from approximately 3,000 individuals will be turned into stem cell lines. These lines will be made available to researchers throughout California and around the world.

Why iPS cells? iPS cells are generated from cells easily obtained from living humans, i.e. blood or a small piece of skin; they have unlimited expansion potential in the petri dish, so huge numbers of cells can be generated for research studies or drug development; and they can be coaxed into the types of cells affected in various diseases, such as heart or brain disorders. This provides an unprecedented opportunity to study the cell types from patients that are affected in disease but cannot otherwise be easily obtained in large quantities from them.

Who is generating the cells? Seven clinician scientists from four California institutions recruit tissue donors who suffer from one of the included diseases or are healthy controls. Some blood or a small piece of skin is collected from those donors, and these samples are shipped to the company Cellular Dynamics International (CDI). CDI generates iPS cells from the samples, and then transfers the iPS cells to the Coriell Institute for Biomedical Research. Coriell operates a cell bank that will distribute the iPS cells to interested researchers at academic and other non-profit institutions, and also to pharmaceutical companies that may want to use them to find new drugs for the diseases that are included in this bank. While CDI and Coriell are located outside California, they have set up facilities at the Buck Institute in Novato, CA, where they generate and bank the iPS cells for this Initiative.

Which diseases will be represented? The stem cell lines created will represent a variety of diseases or conditions that affect brain, heart, lung, liver or eyes. Grantees come from a variety of California-based institutions:

How many samples are being collected? Below is a table that outlines CIRM's collection goalsfor each condition, along with control samples.

* these control donors will be specifically tested for the absence of lung disease

CIRM's New Stem Cell Bank Up, Running (California Healthline)

iPSC Initiative Brochure [PDF] Stem Cell FAQ How do scientists model disease with iPSC's

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Induced Pluripotent Stem Cell Initiative | California's ...

Somatic stem cells in the human endometrium.

By Somatic Stem Cells

The existence of human endometrial somatic stem cells was proposed in the mid-20th century for the first time. This hypothesis became stronger and was revised by two authors between 1978 and 1989. Nevertheless, it was not until 2004 that scientific evidence was first published. As we describe here, the great regenerative capability of the human endometrium has been finally questioned in the last 8 years, and this period can be considered the most productive in endometrial stem cell biology given the new scientific information recapitulated to date. We provide a detailed summary based on the actual scientific knowledge obtained about (1) the existence of somatic stem cells in murine (detected with label-retaining cell methods) and human (cells isolated by different methods) endometria, (2) the involvement of bone marrow as a putative extrauterine source of endometrial somatic stem cells, (3) the implication and biological pathways of these cells in several pathologies like endometriosis and endometrial cancer, and (4) the future of endometrial somatic stem cells in regenerative medicine to provide new strategies in autologous transplant and bioengineering.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Somatic stem cells in the human endometrium.

Miller School of Medicine | University of Miami

By Stem Cell Medical Center

Researchers Innovative Study Links Sustained Poverty to Worse Cognitive Function in Midlife

From left, Adina Zeki Al Hazzouri, Ph.D., with Tali Elfassy, M.S.P.H.

Sustained exposure to economic hardship over two decades was strongly associated with worse cognitive function in relatively young individuals, according to a recent study led by Adina Zeki Al Hazzouri, Ph.D., assistant professor of Epidemiology in the Department of Public Health Sciences at the University of Miami Miller School of Medicine.

Zeki Al Hazzouri, Ph.D., was lead author of the article, Sustained Economic Hardship and Cognitive Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, published recently in the American Journal of Preventive Medicine. Her Miller School co-author was Tali Elfassy, M.S.P.H., a Ph.D. candidate in Epidemiology. The studys co-authors are Stephen Sidney, M.D., M.P.H., of Kaiser Permanente in Oakland, Calif.; David Jacobs, Ph.D., of the University of Minnesota in Minneapolis; Eliseo J. Perez Stable, M.D., of the National Institute of Minority Health and Health Disparities in Bethesda, and Kristine Yaffe, M.D., from the University of California San Francisco.

Read more about the research findings

Christopher B. OBrien, M.D., professor of clinical medicine and medical director of liver, intestinal and multivisceral transplant at the Miami Transplant Institute a unique affiliation between UHealth - the University of Miami Health System and Jackson Health System was the honoree at the second annual Flavors of Miami event in early September.

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Miller School of Medicine | University of Miami

Stem Cell | Makise Medical Center Japan

By Stem Cell Medical Center

Cells develop from only one fertilized egg --- zygote. A "Totipotent Cell" with the ability to differentiate into more than 220 cell types. except placenta. But its Totipotency, (which represents the cell with the greatest differentiation potential) is not retained during all the various stages of cell sub-division.

The first sub-division provides 2 Totipotent cells. The second 4 cells, retain Totipotency But the following 8 cells no longer retain the ability to differentiate into all types of cells. Further sub-divisions differentiate into specialized cells such as fibroblasts, erythrocytes, nerve cells, intestinal mucosal epithelial cells and pancreatic islet cells, etc. but following 6 to 7 full further cell sub-divisions (about 5 days after fertilization), the embryo becomes a "Blastocyst" and possesses "Inner Cell Mass (ICM) "

ICM cells can differentiate into any cell type, except placenta --- pluripotency. 3 weeks after fertilization, the cells of the inner cell mass differentiate into ectoderm, mesoderm and endoderm. In the 1950s, this differentiation was thought to be irreversible, being described as a ball rolling down a hill and technically known as " Epigenetic Landscape".

This was until 1962 when John Gurdon created clone frogs and then in 1996 Ian Wilmut created "Dolly " the cloned sheep. Scientists had previously thought stem cells could not have pluripotency once dispersed into a specialized cell. however, in nature, even once differentiated, some cells can again differentiate and this phenomenon is known to science.

The stem cells of humans have limited ability to differentiate. But for example, Planaria that is a small flatworm living in rivers has amazing ability to differentiate into any organs, even into itself. When it is chopped into 3 fragments like picture, each fragment regenerates to a perfect Planaria. There is a record that 1/279 fragment of one Planaria regenerated to perfect Planarias. When Planaria grows to a certain size, it divides itself to two fragments. And each fragment grows to a perfect Planaria. For Planaria, division and regeneration are mechanism for reproduction. But under some circumstances Planaria chooses sexual reproduction.

A Plant can regenerate itself from one already differentiated cell. An Enzyme mixture of Cellulase Onozuka R-10 and Macerozyme R-10 dissolves tobacco plant (Nicotiana tabacum) leaf cell walls, and cells become leaf protoplasts (= cell without cell walls). When protoplasts are cultivated under appropriate condition, the protoplasts grow to a seedling plant through plant callus (= mass of unorganized parenchyma cells). When the seedling plant is planted in soil, it grows to a perfect tobacco plant.

Two British scientists proved biological technique could change Epigenetic Landscape.

Gurdon created cloned frogs.

Wilmut used a cell nucleus which had been differentiated in the mammary gland.

Human embryos reach "Blastocyst" about 5 days' post fertilization. The Blastocyst possesses an "Inner Cell Mass (ICM) " In 1981 Martin Evans succeeded in culturing mouse ICM cells. These cells are capable of propagating themselves indefinitely in an undifferentiated state, and they can differentiate into any type of cell except placenta. These cells are pluripotent, and known as Embryonic Stem Cell (ES Cells). James Thomson created ES Cells from Monkey embryo in 1995 and later in 1998 created ES Cells from human embryo. However, research into ES Cell needs further study due to an ethical dilemma, that in order to isolate inner cells from the blastocyst, the blastocyst is destroyed, so is the embryo at pre-implantation stage to be considered human? and even if not, do we have the right to destroy human potential growth.

The ethical issue of ES Cells can be by-passed by using Induced pluripotent stem cells. The iPS cell is a pluripotent stem cell which can be generated directly from adult cells, not from human embryos, and in 2006, Shinya Yamanaka and his team in Kyoto University created iPS cells from mouse fibroblasts.

He hypothesized that the genes playing a pivotal role in the function of ES Cells could induce an embryonic state in adult cells. But how many are the genes? The human has 20 - 25 thousand genes. Yamanaka researched and found 24 genes which were important for the characteristic protein of human ES Cells, and then used retroviruses to deliver all 24 genes into mouse fibroblasts, and the fibroblasts were able to propagate indefinitely. These iPS Cells were pluripotent like ES Cells.

Yamanaka removed one factor at a time from the 24 factors to identify the necessary genes for reprogramming and by this process he identified 4 factors -- Oct3/4, Sox2m Klf4 and c-Myc - named the "Yamanaka Factors", and Later he found c-Myc was not needed for reprogramming, but without c-Myc the process took longer and was inefficient.

A strong concern of the iPS researchers was if iPS Cell differentiation caused cancerous cells. But this issue has almost been resolved completely through rigorous study. And many clinical human applications are now carried out in Japan. For example, in 2014 retina transplantation by iPS Cells was successfully carried out for age-related macular degeneration. And cells did not differentiate into cancer cells. In my next page, I write more about these applications.

iPS Cells are useful not just for regenerative medicine but for drug discoveries or development. Because it is very easy for researchers to recreate special cells which cause special diseases, in a petri dish --- Alzheimer's disease, Parkinsons disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia.

For example, "Achondroplasia" which is caused by mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. Researchers made iPS Cells from skin fibroblasts of 3 patients with achondroplasia then allowed the iPS Cells to differentiate into chondrocytes over 2 to 3 weeks. Chondrocytes in the petri dish secreted about themselves an extracellular matrix which is characteristic of chondrocytes and made a mass. Compared to the chondrocytes of healthy people, these patients chondrocytes grew slowly, and the researchers tried thousands of drugs one by one to cure the abnormal chondrocytes from the petri dish specimens. Then finally, and with much surprise, they found the "Statin drug" was effective and able to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are for lowering cholesterol, and nobody expected cholesterol lowering drugs to be effective against achondroplasia.

In the next pages I explain in more detail about practical and clinical uses of iPS Cells.

The researchers of iPS Cells were most afraid of differentiation of iPS Cells into cancer cells. But now this problem has been almost solved by rigorous studies. And many clinical applications for humans are being done in Japan. For example, in 2014 transplantation of iPS Cells of retina was successfully done for age-related macular degeneration in Japan. The cells have not differentiated into cancer cells. In the next page, I write more about the applications.

iPS Cell is very useful not only for regeneration medicine but also for drug discovery or drug development. Because it is very easy for researchers to make the special cells that cause the special diseases --- Alzheimer's disease, Parkinson's disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia -- in petri dish.

For example, Achondroplasia that is caused by a mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. The researchers made iPS Cells from the skin fibroblasts of the 3 patients of achondroplasia and let the iPS Cells differentiate into chondrocytes in 2 to 3 weeks. The chondrocytes in petri dish secreted around themselves an extracellular matrix that is characteristic of chondrocytes and made a mass. The chondrocytes from the patients grow very slow compared with the chondrocytes from those of healthy people. The researchers tried thousands of drugs one by one to cure abnormal chondrocytes from the patients in petri dish. Then finally, and with much surprise, they found "Statin drug" was effective to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are drugs for cholesterol lowering. Nobody expected cholesterol lowering drugs are effective for achondroplasia.

In the next pages, I explain in more detail about practical and clinical use of iPS Cells.

Adult Stem Cells are undifferentiated cells found throughout the body such as in bone marrow, and umbilical cord blood, and the mammary gland, and the surface of the small and large intestines, the adipose tissue, the lining of the nose, the testicles, and the hair follicle, between the basement membrane and the sarcolemma of muscle fibers (Satellite Cells), etc.

These cells are multipotent cells that have less ability to differentiate into specialized cells than pluripotent cells. The adult stem cell from the bone marrow, called Hematopoietic Stem Cell (HSC), was discovered in the 1960s by two Canadian biologists, James Till and Ernest McCulloch, and has been used clinically to cure various blood diseases, such as leukemia, malignant lymphoma, multiple myeloma, etc. Clinically a very important cell. But for regenerative medicine, it needs much practical work to obtain stem cells from bone marrow, and requires general anesthesia, however scientists recently have found it easier to obtain these cells.

This is by ASC (adipose-derived stem cell) from our fat. The first scientific reports on ASC were made by an American scientist, Patricia Zuk (UCLA), in 2001. She reported the presence of mesenchymal stem cells in the fat tissues, and as they have a faster growth rate, these cells are expected to be advantageous for regenerative medicine.

ASC can differentiate into muscle, bone, cartilage, liver, adipose cell (lipid cell). And besides the advantages as stem cell, ASC secrets exsosome (nano size particles) that contain enzymes which dissolve beta-amyloid of Alzheimer's disease. The efficacy is 8 times more potent than the enzymes secreted by the exssome of the bone marrow.

ASC is now aggressively researched in Japan for practical uses. It will be used to treat many diseases such as Alzheimer's, Parkinson's, and diseases of the liver and kidneys, and periodontal disease, and more. For example, please see the video:

In Japan Tottori University Medical School researchers have established the technique of breast reconstruction by ASC after mastectomy due to cancer. They operate and inject ASC into the patients depressed breast. The breast recovers to the original shape within three months. This is not silicon, but the patients own cells. Quite natural. No rejection. The cost of this treatment will be covered by health insurance within three years in Japan. And Doctors at the Nagoya University Medical School use ASC against urinary incontinence stress. The sphincter function of the urethra often weakens due to aging,delivery, and some bladder diseases. ASC is injected around the patients urethra to strengthen the smooth muscle.

However, some side effects may occur by use of ASC. For example, male prostate hyperplasia and female endometriosis. Issues not studied in depth. So for now until the side effects have been dealt with, we should wait for general anti-aging treatments.

Recently it was found possible to induce, directly from somatic cells, not only iPS but nerve cells, hepatocyte cells, myocardium cells, cartilage cells, and many varied cells by introducing the specific key transcription factors in cell differentiation, which means that through by-passing of pluripotent stem cells it is possible to induce differentiated specific cells from somatic cells. This is called "Direct Reprogramming", and the most exciting research for example is: myocardial reprogramming in vivo, where Doctors inject patient's fibroblasts with transcription factors to the infarcted lesion of the heart. There the fibroblasts differentiate into myocardium (heart muscle). So, simple and quick. And this regenerative medical technique is under development mainly in Japan and the United States and as this technique is established, lots of heart surgeries will become obsolete and this is also true of brain surgery. The numbers of hospitals will eventually reduce and cost of time consuming surgeries will lower and this will lead on to a "De-Hospitalized Society".

For a basic understanding of stem cell mechanisms: ES Cell is studied along with iPS Cell and ASC. But ES Cell has an ethical dilemma and this issue shall not be overcome by science. So, it cannot be used for the treatment of human diseases. Direct Reprogramming: Wonderful technology. But it may take 10 or 20 years more to accomplish it. Therefore, at this moment, iPS Cell and ASC are most realistic medical tools for those who are suffering from degenerative diseases and wish rejuvenation.

Go here to see the original:
Stem Cell | Makise Medical Center Japan

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