#Blood to feeling: Mcmaster scientists turn blood into neural cells Adult sensory neurons made from human patients blood samplescientists at Mcmaster University have discovered how to make adult sensory neurons from human patients simply by having them roll up their sleeve and providing
was led by Mick Bhatia, director of the Mcmaster Stem Cell and Cancer Research Institute. He holds the Canada Research Chair in Human Stem Cell biology
In extreme conditions, pain or numbness is perceived by the brain using signals sent by these peripheral nerves. he problem is that unlike blood, a skin sample or even a tissue biopsy,
and make the main cell types of neurological systems the central nervous system and the peripheral nervous system in a dish that is specialized for each patient,
as routinely performed in a doctor office, and with it we can produce one million sensory neurons,
adding that it allows researchers to start asking questions about understanding disease and improving treatments such as:
Can the neuropathy that diabetic patients experience be mimicked in a dish? It also paves the way for the discovery of new pain drugs that don just numb the perception of pain.
or experiencing neuropathy, the prized pain drug for me would target the peripheral nervous system neurons, but do nothing to the central nervous system,
or neuropathy to run tests on neurons created from blood samples of patients taken in past clinical trials where responses
in that one might be able to look at a patient with Type 2 Diabetes and predict whether they will experience neuropathy by running tests in the lab using their own neural cells derived from their blood sample. his bench to bedside research is very exciting
and will have a major impact on the management of neurological diseases, particularly neuropathic pain, said Akbar Panju, medical director of the Michael G. Degroote Institute for Pain Research and Care,
a clinician and professor of medicine. his research will help us understand the response of cells to different drugs and different stimulation responses,
and allow us to provide individualized or personalized medical therapy for patients suffering with neuropathic pain. ource:
Mcmaster Universit i
#Controlling a robotic arm with a patient intentions Giving himself a drink for the first time in 10 years,
or paralysis to control the movement of a robotic limb one that can be connected either to
In a clinical trial, the Caltech team and colleagues from Keck Medicine of USC have implanted successfully just such a device in a patient with quadriplegia
High spinal cord injuries can cause quadriplegia in some patients because movement signals cannot get from the brain to the arms and legs.
As a solution, earlier neuroprosthetic implants used tiny electrodes to detect and record movement signals at their last stop before reaching the spinal cord:
the Caltech team collaborated with surgeons at Keck Medicine of USC and the rehabilitation team at Rancho Los Amigos National Rehabilitation Center.
The surgeons implanted a pair of small electrode arrays in two parts of the PPC of a quadriplegic patient.
After recovering from the surgery, the patient was trained to control the computer cursor and the robotic arm with his mind.
since his injury that he could move a limb and reach out to someone. It was a thrilling moment for all of us,
such as those of the Andersen Lab at Caltech, to human patients, ultimately turning transformative discoveries into effective therapies, says center director Charles Y. Liu, professor of neurological surgery, neurology,
and biomedical engineering at USC, who led the surgical implant procedure and the USC/Rancho Los Amigos team in the collaboration. n taking care of patients with neurological injuries and diseasesnd knowing the significant
Dr. Mindy Aisen, the chief medical officer at Rancho Los Amigos who led the study rehabilitation team,
We have created a unique environment that can seamlessly bring together rehabilitation, medicine, and science as exemplified in this study,
it like going to the dentist and having your mouth numbed. It very hard to speak without somatosensory feedback.
These people accumulate numerous self-inflicted injuries often leading to reduced lifespan. Using detailed genome mapping,
The team looked at nerve biopsies taken from the patients to see what had gone wrong and found that particular pain-sensing neurons were absent.
From these clinical features of the disease, the team predicted that there would be a block to the production of pain-sensing neurons during the development of the embryo they confirmed this using a combination of studies in mouse and frog models,
says Professor Geoff Woods from the Cambridge Institute for Medical Research at the University of Cambridge,
particularly given recent successes with drugs targeting chromatin regulators in human disease, adds Dr Ya-Chun Chen from the University of Cambridge,
as well as disease/drought resistance that also include the bread-quality gene, he said. sing the speed-breeding technology developed by QAAFI Dr Lee Hickey,
portable and economic biosensing device that allows for immediate diagnostic testing of arthritis, cystic fibrosis, acute pancreatitis and other clinical diseases.
clinically relevant biomarkers found in high concentration in many human diseases. he samples were placed on the tablet
The researchers believe that the device has enormous potential for use in point-of-care medical diagnostics,
Goldys believes that we will see rapidly increasing use of smartphone technology in the field of biomedical diagnostics, particularly in resource poor areas.
and lead author and graduate student J. Sherry Wang applied their new molecular tools to 44 DNA samples with known cancer-related single-nucleotide variants.
as a significant step toward advancing personalized medicine. The ability to accurately find mutations that are biomarkers for disease will help clinicians determine treatment paths for patients,
Zhang said. It may also help identify rare mutations and subtypes of infectious diseases as well as drug-resistant strains.
A single-nucleotide variant occurs when one of the four basic components that make up DNA
but mutations can leave the body vulnerable to disease, or even be the root cause.
The ability to accurately find rare single-nucleotide mutations is becoming increasingly important as scientists drill down into genomes to find biomarkers for early cancer detection. ee trying to solve the needle-in-a-haystack problem,
The needle youe looking for might be a cancer-mutation DNA or bacterial-pathogen DNA,
when there not as much cancer DNA floating around, he said
#Nearly Indestructible Virus Yields Tool to Battle Diseases By unlocking the secrets of a bizarre virus that survives in nearly boiling acid,
scientists at the University of Virginia School of medicine have found a blueprint for battling human disease using DNA clad in near-indestructible armor.
Edward H. Egelman with the massive Titan Krios microscope that buried in tons of concrete under Fontaine Research Parkhat interesting and unusual is being able to see how proteins
. But that protective mechanism becomes a major obstacle for doctors seeking to use genes to battle disease.
very horrific diseases that are hard to treat, like anthrax, Egeleman said. o we show in this paper that this virus actually functions in a similar way to some of the proteins present in bacterial spores. pores are formed also by C. difficile,
which now accounts for approximately 30,000 deaths per year in the U s. and has been classified by the Centers for Disease Control
It is the first time that a phase III trial of viral immunotherapy has shown definitively benefit for patients with cancer.
The trial was led in the UK by researchers at The Institute of Cancer Research, London,
inoperable malignant melanoma to receive either an injection of the viral therapy, called Talimogene Laherparepvec, or a control immunotherapy.
a mark oncologists often use as a proxy for cure in immunotherapy. Importantly, responses to treatment were pronounced most in patients with less advanced cancers (stage IIIB, IIIC,
IVM1A) and those who had yet to receive any treatment underlining the potential benefits of T-VEC as a first-line treatment for metastatic melanoma
which cannot be removed surgically. Patients with stage III and early stage IV melanoma treated with T-VEC a total of 163 people lived an average of 41 months.
This compared with an average survival of 21.5 months in the 66 earlier-stage patients who received the control immunotherapy.
and is published in the Journal of Clinical Oncology. T-VEC is modified a form of herpes simplex virus type-1
T-VEC is one of a new wave of virus-based drugs to show benefits in cancer trials,
because their infection defences are compromised by genetic errors. UK trial leader Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, London,
here is increasing excitement over the use of viral treatments like T-VEC for cancer,
or some of the other new immunotherapies. ur study showed that T-VEC can deliver a significant, durable benefit for people with melanoma.
It is encouraging that the treatment had such a clear benefit for patients with less advanced cancers ongoing studies are evaluating
if it can become a first-line treatment for more aggressive melanomas and advanced disease. rofessor Paul Workman,
Chief executive of The Institute of Cancer Research, London, said: e may normally think of viruses as the enemies of mankind,
and kill human cells that can make them such promising cancer treatments. In this case we are harnessing the ability of an engineered virus to kill cancer cells
and there is hope that therapies like this could be even more effective when combined with targeted cancer drugs to achieve long term control
#A novel source of multipotent stem cells for the treatment of autologous reproductive tract injury The utility of human fallopian tube mucosa as a novel source of multipotent stem cells for the treatment
and we also compared multipotent stem cells derived from fallopian tubes and fallopian tube mucosa according to their biological characteristics and therapeutic potential for treatment of autologous reproductive tract injury.
which make them a better source of stem cells for the treatment of autologous reproductive tract injury.
what causes immune cell migration to wounds Immune cells play an important role in the upkeep
and repair of our bodies, helping us to defend against infection and disease. Until now, how these cells detect a wounded
could help scientists design therapies to manipulate the cell repair process and direct immune cells away from sites where they are doing damage,
ingest and degrade debris, dying cells and invading pathogens. After dissecting the signaling occurring in immune cells responding to wound induced (H2o2),
, in Bristol School for Cellular and Molecular Medicine, and the study lead author, said: hile inflammation is critical to prevent infection,
too much of a response by immune cells can cause or worsen a wide range of human diseases
and conditions including autoimmunity, atherosclerosis, cancer and chronic inflammation. his research is therefore critical for improving human health as it enables us to discover novel points of intervention to manipulate immune cell behaviour
and allow us to design therapies to direct immune cells away from sites where they are doing damage
and send them into places where they are needed. y
#First successful study of virus attack on cancer It a new weapon in the arsenal of cancer fighting treatments:
utilizing genetically modified viruses to invade cancer cells and destroy them from the inside. University of Louisville researcher Jason Chesney, M d.,Ph d.,deputy director of the James Graham Brown Cancer Center (JGBCC),
and a team of international scientists found that stage IIIB to IV melanoma patients treated with a modified cold sore (herpes virus had improved survival.
The results of the findings were published recently in the Journal of Clinical Oncology. Uofl was one of the major sites for the phase III clinical trial involving 436 patients who received the viral immunotherapy, talimogene laherparepvec (T-VEC.
Scientists genetically engineered the herpes simplex I virus to be non-pathogenic, cancer-killing and immune-stimulating.
The modified herpes virus does not harm healthy cells, but replicates when injected into lesions or tumors,
and then stimulates the body immune system to fight the cancer. he results from this study are said amazing,
Chesney. atients given T-VEC at an early stage survived about 20 months longer than patients given a different type of treatment.
For some, the therapy has lengthened their survival by years. hari Wells from Ashland, Kentucky is one of those patients.
or metastatic, melanoma. Before entering the T-VEC trial, she had been through numerous procedures and major surgeries.
Dr. Chesney and the James Graham Brown Cancer Center saved my life. ells drove to Louisville every two weeks for about two
and a half years to receive injections in each of the more than 60 lesions on her leg.
The lesions eventually began to fade and finally disappeared. She has been in remission for almost three years. want everyone to know they should never give up hope.
The U s. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are considering findings from the trial to make the treatments available to more patients with advanced melanoma.
More Researchthe Journal of Clinical Oncology report comes on the heels of Chesney findings from another study published this month in the New england Journal of Medicine.
The article describes an immunotherapy for melanoma utilizing the checkpoint inhibitors, ipilimumab and nivolumab. In cell biology
The study found that injection of the two inhibitors shrunk tumors in the majority of patients with advanced melanoma.
and find that ipilimumab combined with nivolumab resulted in the highest anticancer efficacy ever observed after treatment with a cancer immunotherapy.
and other sites in hopes of accelerating cancer immunity and curing patients. e finally understand how to activate the human immune system to clear cancer cells,
having developed new classes of immunotherapies that dramatically improve the survival of cancer patients, Chesney said. believe T-VEC combined with immune checkpoint inhibitors will not only reduce cancer-related mortality in melanoma but in all cancer types,
and we are moving quickly to develop these methods. ource: Uof e
#Researchers retrieve ostmemories Retrograde amnesia is the inability to recall established memories. In humans, amnesia is associated with traumatic brain injury, Alzheimer disease,
and other neurological conditions. Whether memories lost to amnesia are erased completely or merely unable to be recalled remains an open question.
Now, in a finding that casts new light on the nature of memory, published in Science,
researchers from the RIKEN-MIT Center for Neural Circuit Genetics demonstrated in mice that traces of old memories do remain in the amnestic brain,
and that the cellular pathways underlying them can be reactivated, allowing lost memories to be found.
whose storage was disrupted by chemically inducing retrograde amnesia, could still be recalled. rain researchers have been divided for decades on
whether amnesia is caused by an impairment in the storage of a memory, or in its recall, said Tonegawa.
thus inducing retrograde amnesia. Other mice received saline as a control. As expected, amnestic mice returned to chamber A did not freeze,
despite the induction of retrograde amnesia, the authors suggest that different processes may control memory encoding and recall.
says Tonegawa, s that in retrograde amnesia, past memories may not be erased, but could simply be lost and inaccessible for recall.
and save thousands of dollars per transplant. UCLA researchers measured liver function in 53 potential organ donors using the fingertip probe.
In the study, it successfully predicted every time which livers would function properly in transplant patients,
the study first author and an assistant professor of surgery in UCLA division of liver and pancreas transplantation. his device is best single predictor of organ survival in our patients,
Larger scale gene function studies A relatively new method of targeting specific DNA sequences in zebrafish could dramatically accelerate the discovery of gene function and the identification of disease genes in humans, according to scientists at the National Human genome Research
or have been identified as possible disease genes, but the functions of those genes have not been confirmed by knocking them out in animal models and seeing
Dr. Burgess said. he study of zebrafish has led already to advances in our understanding of cancer
and other human diseases, said NHGRI Director Eric Green, M d, . Ph d. e anticipate that the techniques developed by NHGRI researchers will accelerate understanding the biological function of specific genes
and the role they play in human genetic diseases. The CRISPR/Cas9 method of gene editing is one of the two essential components in the NHGRI team high-throughput method.
of which are similar to human genes involved in deafness. Hearing is one of the other interests of Dr. Burgess lab.)This produced mutations in 82 of the 83 genes.
#Injectable electronics New system holds promise for basic neuroscience, treatment of neurodegenerative diseasesit a notion that might be pulled from the pages of science-fiction novel electronic devices that can be injected directly into the brain,
and treat everything from neurodegenerative disorders to paralysis. It sounds unlikely, until you visit Charles Lieber lab. A team of international researchers, led by Lieber, the Mark Hyman, Jr.
would it be possible to deliver the mesh electronics by syringe needle injection, a process common to delivery of many species in biology and medicine you could go to the doctor
and you inject this and youe wired up.''hough not the first attempts at implanting electronics into the brain deep brain stimulation has been used to treat a variety of disorders for decades the nano-fabricated scaffolds operate on a completely different scale. xisting techniques are crude relative
and administered like any other injection. After injection, the input/output of the mesh can be connected to standard measurement electronics
so that the integrated devices can be addressed and used to stimulate or record neural activity. hese type of things have never been done before, from both a fundamental neuroscience and medical perspective,
Lieber said. t really exciting there are a lot of potential applications. oing forward, Lieber said, researchers hope to better understand how the brain
and Applied science and California Nanosystems Institute has identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
the multidisciplinary team also included Michel Gilliet of Switzerland Lausanne University Hospital, and Jure Dobnikar and Daan Frenkel of the University of Cambridge.
Autoimmune diseases strike when the body attacks itself because it fails to distinguish between host tissue
and disease-causing agents, or pathogens. Two such disorders are lupus, which can damage the skin, joints and organs, causing rashes, hair loss and fatigue;
and psoriasis, which causes rashes, lesions and arthritis, and creates an increased risk for cancer and diabetes.
When a healthy person is infected by a virus, VIRAL DNA can activate immune cells via a receptor called TLR9.
The receptor triggers the cells to send signaling molecules called interferons to initiate a powerful defensive response.
In people with lupus or psoriasis, these cells are activated by their own DNA, or self-DNA.
Using synchrotron X-ray scattering and other techniques, researchers determined that a broad range of molecules,
Wong said. his new knowledge will make it easier to design new therapeutic strategies to control immune responses.
and triggering responses in disorders such as lupus and psoriasis. We were able to elucidate something that was understood poorly a key to triggering the immune response is that the molecules must arrange the DNA
reduce agility and result in fatigue, joint sprains or long-term ailments like arthritis or chronic back problems.
ETOWL measures the stress placed on each avatar joints as well as its balance, flexibility and center of gravity.
Squire believes this will prevent future injuries and reduce the time and financial cost of unnecessary field trials.
The polymer is known as Ropy 352 and produced by a non-disease-causing bacterium. his is one of many naturally occurring,
non-disease-causing bacterial strains my research program isolated and studied for years, said Janine Trempy,
In basic research, wee also broadened our understanding of how and why non-disease-causing bacteria produce polymers.
non-disease-causing bacterial strains that produce unique polymers with characteristics desirable and safe for food products,
These are driven chemical processes by naturally occurring bacteria that do not cause disease in humans, Trempy said,
but is derived from a bacterium known to be a plant pathogen and suspected of causing digestive distress
or fever-inducing. Trempy research program has determined the new polymer will thicken whole and nonfat milk,
#Petri dish tumor test could personalize drug therapy for cancer patients In a highly successful, first-of-its-kind endeavor,
The advance could mean a giant step forward in efforts to tailor medical treatment plans to individual patients.
Led by Shigeki Miyamoto, a professor of oncology at UW-Madison, and David Beebe, the John D. Macarthur Professor and Claude Bernard professor of biomedical engineering at UW-Madison, the researchers published news of the advance May 1, 2015, in the Royal Society
which involves co-culturing multiple myeloma tumor cells with their surrounding nontumor cells, all from the same patient, in a microscale petri dish.
The researchers then treated the tumor cells with bortezomib, a drug commonly used in multiple myeloma therapy.
And after only three days, the researchers could determine whether the drug was effective or not.
Multiple myeloma is a universally fatal cancer. Rising in the blood marrow due to an accumulation of abnormal,
or cancerous, plasma cells, myeloma is treatable but incurable. he median survival rate has improved, but is only about five to seven years,
The new assay could save many multiple myeloma cancer patients the psychological stress of having to try multiple drugs until they find the most effective one.
The fundamental idea behind the research was to focus on everything surrounding a tumor not just the tumor itself.
These surroundings can include bone marrow stromal cells, macrophages and other immune cells, all of which represent an integral part of the tumor environment.
By including these components in a microfluidic petri dish a device developed by Beebe and Miyamoto lab a few years ago the researchersability to accurately gauge results increased dramatically.
The researchers essentially created a miniaturized external model of an individual cancer, says Pak. She has founded a service-based company called Lynx Biosciences based on these findings,
In addition, they are starting to consider what this discovery means for other cancer types and other drugs.
The researchersresults could have interesting and wide-ranging implications for the future of cancer treatment and therapy,
although their work is far from over. his is only one type of cancer, one particular drug,
The engineered organ has implications for everything from rapid production of immune therapies to new frontiers in cancer or infectious disease research.
Germinal centers are a sign of infection and are not present in healthy immune organs.
the organ could be used to study specific infections and how the body produces antibodies to fight those infections from Ebola to HIV. ou can use our system to force the production of immunotherapeutics at much faster rates,
he said. Such a system also could be used to test toxic chemicals and environmental factors that contribute to infections or organ malfunctions.
The process of B cells becoming germinal centers is understood not well, and in fact, when the body makes mistakes in the genetic rearrangement related to this process,
blood cancer can result. n the long run, we anticipate that the ability to drive immune reaction ex vivo at controllable rates grants us the ability to reproduce immunological events with tunable parameters for better mechanistic understanding of B cell development and generation of B cell tumors,
as well as screening and translation of new classes of drugs, Singh said g
#New drug triggers tissue regeneration: Faster regrowth and healing of damaged tissues Research focuses on select tissues injured through disease, surgery and transplants,
but early findings indicate potential for broad applicationsthe concept sounds like the stuff of science fiction:
Researchers at Case Western Reserve and UT Southwestern Medical center this week announced that they have taken significant steps toward turning this once-improbable idea into a vivid reality.
the Ingalls Professor of Cancer Genetics at the university School of medicine and a medical oncologist at University Hospitals Case Medical center Seidman Cancer Center. e have developed a drug that acts like a vitamin for tissue stem cells,
which suggests to us that it may have applications in treating many diseases. he institutions collaborating on this work next hope to develop the drug now known as W033291for use in human patients.
they first would focus on individuals who are receiving bone marrow transplants, individuals with ulcerative colitis, and individuals having liver surgery.
The goal for each is the same: to increase dramatically the chances of a more rapid and successful recovery.
Zhang then traveled to UT Southwestern Harold C. Simmons Comprehensive Cancer Center where Willson serves as director.
The third finding came through collaboration between Markowitz and Stanton L. Gerson, MD, director of the Case Comprehensive Cancer Center, UH Seidman Cancer Center,
as well as the Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological Oncology. Case Western Reserve research associate Amar Desai, Phd, worked between the Markowitz
and then received a partial bone marrow transplant. Without SW033291, the animals died. With it they recovered.
From there, more detailed studies showed that mice given SW033291 recovered normal blood counts six days faster than mice that were transplanted without receiving SW033291.
Neutrophils battle infection, platelets prevent bleeding, and red blood cells deliver oxygen throughout the body. In addition, Desai work showed that
When investigators treated mice with other diseases the SW033291 drug again accelerated tissue recovery. For example, the investigators teamed with Fabio Cominelli, MD, Phd, a Case Western Reserve Professor and Chief of the Division of Gastroenterology and Liver disease,
to study a mouse model of ulcerative colitis. SW033291 healed virtually all the ulcers in the animalscolons
and prevented colitis symptoms. In mice where two-thirds of their livers had been removed surgically, SW033291 accelerated regrowth of new liver nearly twice as fast as normally happens without medication.
Because bone marrow, colon, and liver are significantly different tissues, the investigators believe the pathway by which SW033291 speeds tissue regeneration is likely to work as well for treating diseases of many other tissues of the body.
However the next stages of the research will concentrate on three diseases where SW033291 already shows promise to provide dramatic improvement.
In bone marrow transplants, for example, effects of SW033291 in accelerating tissue growth would provide the body the cells required to fight off the two most common and sometimes fatal complications, infection and bleeding.
For those suffering the debilitating impact of colitis, accelerating tissue growth could heal colon ulcers more quickly,
which in turn could allow patients to take lower dosages of other medications that treat colitis some
of which have serious side effects. Finally, the promise of tissue growth could increase survival rates for patients with liver cancer;
in some cases today, physicians are unable to perform surgery because the amount of the liver to be removed would be so great as to pose severe risk to the patient.
But having a drug to accelerate the liver regrowth could make surgery a viable option.
The team next step will be to complete studies showing safety of SW033291-related compounds in larger animals, a required part of the pathway to secure approval from the U s. Food and Drug Administration
from the Harrington Discovery Institute at University Hospitals, and from multiple National institutes of health grants that included the Case GI SPORE,
and the National Center for Accelerating Innovation at the Cleveland Clinic. Additional support was received from the Marguerite Wilson Foundation;
the Cancer Prevention & Research Institute of Texas; Inje University; and the Korean National Research Foundation.
Markowitz and Willson, former director of the Case Comprehensive Cancer Center and now director of the Simmons Cancer Center at UT Southwestern, initiated the project to study the potential of inhibiting 15-PGDH as a tissue
Yang and Bae, now at Inje University in Korea, worked in the Markowitz laboratory on studies of colitis (Yang) and on liver regrowth after surgery (Bae.
Fink and Tiwari, both of Case Western Reserve, completed the work on the colitis mouse model.
who played a role in the success of the colitis experiments in mice, and Mark Chance, who contributed proteomics expertise for studies that showed how SW033291 works.
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