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What impact will Covid-19 have on the biotech sector? – Investment Week

Posted: April 16, 2020 at 9:46 pm

Carl Harald Janson of the International Biotechnology Trust

After a torrid three weeks, financial markets stabilised in recent days in response to the stimulus packages announced both by central banks and governments.

This steadying of performance will enable investors to take a more rational and considered approach.

The impact of quarantines required to bring Covid-19 under control will have profound economic ramifications and while certain sectors will bear the brunt of this hardship, others will play a significant role in helping society to navigate this pandemic.

The race for a vaccine: The investment trust managers combating coronavirus

The biotechnology sector will be integral in developing both treatments and vaccines to control the disease. Some healthcare companies will contribute to the responses to this virus or maintain their existing drug sales while others will see their business models under threat.

One company that should help to control the pandemic is the US biotechnology giant Gilead. It specialises in anti-viral therapies and it has a number of drugs used to treat HIV and a blockbuster therapy for Hepatitis C.

Gilead's experimental drug, remdesivir, is currently undergoing multiple late-stage clinical trials as a potential treatment of Covid-19.

This anti-viral drug was previously tested in humans with ebola and has shown promise in trials of other diseases caused by coronaviruses.

If the drug is shown to be safe and effective for the treatment of Covid-19, it is likely to receive accelerated regulatory approval.

In addition, the company has considerable cash reserves which will help weather any adverse impacts if either remdesivir proves not to be effective or sales of its other drugs falter.

Concept stocks: An opportunity for short sellers

It is not only companies involved directly in the battle against Covid-19 which are likely to continue positively contributing to society.

Genmab has a drug used to treat multiple myeloma. As there is unmet medical need for this condition, patients will continue with this therapy, irrespective of a global downturn.

In addition, the company is profitable and cash generative making it a safe haven for investors.

Another such company is Vertex, which has an oral treatment for patients suffering from cystic fibrosis, enabling them to avoid visiting a hospital at this dangerous time.

This chronic condition will need continuous treatment, which protects the sales of this drug.

Contract research organisations will, however, struggle in the current environment as many clinical trials will be halted as the people operating these medical explorations go into lockdown.

Those companies with limited cash reserves will also be hit hard as they will quickly run out of funds and will find it difficult to raise additional money given the current uncertainty.

Companies providing drugs which are mainly used by the elderly but are not essential, such as treatments for glaucoma and osteoporosis, may see sales falter as this vulnerable patient population avoids doctors' surgeries.

In light of the current situation, the relationship between the healthcare industry and President Donald Trump's administration might change. His re-election chances are dependent on how the pandemic and the economic downturn is handled.

If re-elected, Trump is less likely to clamp down heavily on future drug pricing if the biotech sector has enabled him to control the crisis and get the economy back on track.

Nor is it likely that Joe Biden would, if elected, erode healthcare profit margins as the sector will have helped the US to win the war against Covid-19.

Carl Harald Janson is lead investment manager of the International Biotechnology Trust

A stabilisation in financial markets will help investors act more rationally and select those sectors making a positive contribution.

Biotechnology companies that can develop either treatments or vaccines should perform well, so should those companies whose drug sales will continue despite most healthcare systems being overwhelmed by the treatment of this virus

Bear points

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Here is why PDS Biotechnology Corporation (PDSB) stock volatility recorded over the last month was 17.46% – The InvestChronicle

Posted: April 16, 2020 at 9:46 pm

Lets start up with the current stock price of PDS Biotechnology Corporation (PDSB), which is $1.22 to be very precise. The Stock rose vividly during the last session to $1.62 after opening rate of $1.01 while the lowest price it went was recorded $1.01 before closing at $0.83.

PDS Biotechnology Corporation had a pretty Dodgy run when it comes to the market performance. The 1-year high price for the companys stock is recorded $9.45 on 05/15/19, with the lowest value was $0.62 for the same time period, recorded on 04/02/20.

Price records that include history of low and high prices in the period of 52 weeks can tell a lot about the stocks existing status and the future performance. Presently, PDS Biotechnology Corporation shares are logging -87.08% during the 52-week period from high price, and 98.39% higher than the lowest price point for the same timeframe. The stocks price range for the 52-week period managed to maintain the performance between $0.62 and $9.45.

The companys shares, operating in the sector of healthcare managed to top a trading volume set approximately around 16.77 million for the day, which was evidently higher, when compared to the average daily volumes of the shares.

When it comes to the year-to-date metrics, the PDS Biotechnology Corporation (PDSB) recorded performance in the market was -68.68%, having the revenues showcasing -68.08% on a quarterly basis in comparison with the same period year before. At the time of this writing, the total market value of the company is set at 12.68M, as it employees total of 15 workers.

According to the data provided on Barchart.com, the moving average of the company in the 100-day period was set at 1.8275, with a change in the price was noted -0.9400. In a similar fashion, PDS Biotechnology Corporation posted a movement of -42.34% for the period of last 100 days, recording 277,945 in trading volumes.

Total Debt to Equity Ratio (D/E) can also provide valuable insight into the companys financial health and market status. The debt to equity ratio can be calculated by dividing the present total liabilities of a company by shareholders equity. Debt to Equity thus makes a valuable metrics that describes the debt, company is using in order to support assets, correlating with the value of shareholders equity. The total Debt to Equity ratio for PDSB is recording 0.00 at the time of this writing. In addition, long term Debt to Equity ratio is set at 0.00.

Raw Stochastic average of PDS Biotechnology Corporation in the period of last 50 days is set at 31.88%. The result represents downgrade in oppose to Raw Stochastic average for the period of the last 20 days, recording 66.16%. In the last 20 days, the companys Stochastic %K was 67.22% and its Stochastic %D was recorded 54.64%.

Lets take a glance in the erstwhile performances of PDS Biotechnology Corporation, multiple moving trends are noted. Year-to-date Price performance of the companys stock appears to be encouraging, given the fact the metric is recording -68.68%. Additionally, trading for the stock in the period of the last six months notably deteriorated by -74.77%, alongside a downfall of -86.93% for the period of the last 12 months. The shares increased approximately by 0.46% in the 7-day charts and went up by 13.82% in the period of the last 30 days. Common stock shares were lifted by -68.08% during last recorded quarter.

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Orgenesis to acquire assets of Tamir Biotechnology and its anti-viral platform ranpirnase for $19M – Proactive Investors USA & Canada

Posted: April 16, 2020 at 9:46 pm

Orgenesis plans to combine ranpirnase with its Bioxome technology for enhanced payload delivery directly to cells

Inc () has entered into an agreement to acquire the assets of Tamir Biotechnology Inc including its broad-spectrum anti-viral platform ranpirnase.

The acquisition will be completed for total stock and cash consideration valued at about $19 million based on the value of the stock at closing, according to a statement.

Orgenesis said it plans to combine ranpirnase with its co-developed Bioxome technology for enhanced payload delivery directly to cells.

TamirBio is a clinical stage anti-viral therapeutics company engaged in the discovery and development of a new class of prophylactic and therapeutic drugs for the treatment of viruses and other pathological conditions.

TamirBios ranpirnase, its lead asset, is a ribonuclease (RNase),a member of the superfamily of enzymes that catalyze the degradation of RNA, and mediate several essential biological activities, including the regulation of cell proliferation, maturation, differentiation, and cell death.

Orgenesis said it is a potential candidate for the development of therapeutics for life-threatening diseases, including viral and autoimmune diseases, that require anti-proliferative and apoptotic properties.

TamirBios first target is the human papilloma virus (HPV), the worldwide leading cause of genital warts. The companys lead asset, topical ranpirnase, was evaluated in a Phase I/II clinical trial targeting genital warts. The Phase I/II study demonstrated the clear clinical effect of ranpirnase. Additional clinical trials are currently being planned.

Orgenesis and TamirBio plan to combine ranpirnase with Bioxomes, which have demonstrated the ability to fuse with cell membranes and deliver an intracellular cargo, in a similar manner to natural exosomes.

Bioxomes can carry selected therapeutic cargo inside the target cells when loaded with predesignated genetic material, proteins, signaling molecules and drugs, as these mimic the natural membrane fusion capacity of exosomes. Orgenesis and TamirBio believe the combination of the two platforms will result in enhanced efficacy and anti-viral results.

READ:Orgenesis and ExcellaBio develop a breakthrough manufacturing process for bioxomes

Combining TamirBios broad antiviral platform, ranpirnase, with Bioxomes could result in an enhanced payload delivery into cells, said Orgenesis CEO Vered Caplan.

In independent third-party testing, ranpirnase has shown anti-viral activity in multiple viruses. Additionally, over 1,000 patients have been dosed with ranpirnase in previous cancer/mesothelioma clinical trials. Ranpirnase demonstrated a strong safety and tolerability profile that should help accelerate the approval pathway.

Caplan added: We believe combining ranpirnase with the Bioxome platform has the potential to become a potent and powerful combination given the natural intracellular trafficking abilities of Bioxomes. We look forward to testing a variety of additional anti-viral therapies in the near future.

Jamie Sulley, president of TamirBio, pointed out that ranpirnase has already demonstrated preclinical antiviral activity in such viral diseases as HPV, HIV, Ebola, and SARS.

Not only do we believe Orgenesis will help advance ranpirnase through the clinic using their global development platform, but by combining ranpirnase with the Bioxome technology, we believe we can deliver ranpirnase through a more effective delivery mechanism, Sulley said.

Germantown, Maryland-based Orgenesis is a vertically integrated biopharmaceutical company with expertise in developing advanced cell therapies and manufacturing.

Contact the author: [emailprotected]

Follow him on Twitter @PatrickMGraham

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The Book of You: Creating a Story of Health Through Epigenetics – Thrive Global

Posted: April 16, 2020 at 9:43 pm

AncestryDNA, 23 and Me, National Geographic Geno 2.0..today so many of us turn to genetic testing to nd out more about ourselves. While some of us search our genetic code to discover where our ancestors began; others are turning to genetic testing to reveal health concerns which may lay hidden in the spirals and twists of our DNA. Problems can arise then when we mistake our new-found information about what is written in our genes with how our health will be in the future.

Recent studies reveal that a better predictor of future health lies in our epigenes.

EPIGENETICS: the study ofthe process by which genetic information istranslated into thesubstance andbehavior of an organism: specically, the study of the way in which the expression ofheritable traits is modied by environmental inuences or other mechanisms without a change to the DNA sequence.

Simply put, our environment aects the expression of our genes. To illustrate this, lets imagine The Book of You.

Your prologue contains snippets of your parents, their well being, and the quality of combined DNA which they passed to you via egg and sperm. It contains the struggles they encountered, the foods they ate, and the adaptations of their genetic material as they coped with their environments over millennia.

All of this pre-work isnt YOU yet. It is back ground information which has been collected from your families DNA library. The rst page in The Book of You begins at conception.

CONCEIVE: 1) to become pregnant 2) to form in themind; to imagine.

The dualistic nature of conception as both a physical event and a metaphysical event, represents the magic that begins The Book of You. We are both body and spirit by design. Our physical conception in the womb underlies the divine conception of our soul when we were thought onby Creation itself. We operate in a body that eats, sleeps, works, plays, and reproduces in a physical realm; while at the same time we laugh, cry, hope, believe, and dream in a spirit that exists in a metaphysical realm.

Our health at birth appears as a reection of our environment during time spent in the womb. As a tiny sentient being, you responded to your mothers voice, and dwelt in the mystical darkness beneath her heart. You heard the rhythmical beat of her heart sending oxygenated blood to her body; and oated in the hammock of her body as she moved throughout her day. Maybe you heard her singing and felt her laughter. Her body gave you your rst nourishment, delivered through the placenta. Your wellbeing was entirely dependent on the wellbeing of your mother, and life was good.

Or not. Maybe your mother suered from stress or depression. Perhaps she lived in poverty, and was physically abused. Cloaked in her body, you felt her body tighten around you. You heard her cry and scream. You felt her stumble and fall. Maybe your mother retreated to drugs or alcohol. Your tiny body became accustomed to the rush of chemicals as they washed through your system. Here lies the story of epigenetic expression, and how it can shape our very beginning.

The magical truth about epigenetic expression is that it can be changed. For the sake of simplicity, your epigenes are electrons, that act like tiny protein switches that can turn on or turn o the expression of your DNA. These protein switches are only visible on a quantum level when you look at them, then they disappear as you look away because they are made of energy.The energy to form our epigenes is generated from food, nutrients, and thought.

This is how our environment aects our epigenetic expression: if we are in an environment, rich with organic foods, healthy relationships, and pleasant surroundings, we produce healthy epigenes that switch our DNA to health. However, if we are eating heavily processed foods, living with abusive relationships, immersed in stressful surroundings, we produce unhealthy epigenes that switch our DNA to disease.

Two of the fastest ways to start repairing our DNA and to switch our genes to health is through liposomal bovine colostrum and mind/body practices.

Because liposomal colostrum is the rst food of life for all mammals, it is the most perfect food to rebuild healthy genetic expression. It gives us all the necessary building blocks needed to form our internal environment. Liposomal colostrum is bio-identical to human colostrum, and enables us to utilize colostrum therapeutically. Two very important components of liposomal colostrum are immune factors and growth factors.

Immune factors in liposomal colostrum include lactoferrin, proline-rich peptides, leukocytes, cytokines, oligo polysaccharides and immunoglobulins. These target harmful bacteria and viruses. While harmful bacteria and viruses create a stressful environment in our microbiome, liposomal colostrum replaces the harmful bacteria with healthy bacteria, changing our internal environment to one of health.

As we are constantly regenerating cells, the growth factors in colostrum encourage healthy expression of epithelial cells, broblasts, hormones, and platelets.

Our power of thought may be the most over looked tool in determining healthy gene expression. Thoughts and emotions create proteins in our epigenetic electrons, and happy, positive thoughts create healthy epigenes. Throughout millennia, it has been observed that when we think we are receiving a medicine, we often get better. Its called the placebo eect, and has been documented throughout medical literature.

So as we re-write our Book of You, from a story that may hold health concerns in the DNA of our prologue, it is important to remember that we control the pen while writing the story of our health. Choosing healthy, organic foods, and forming healthy relationships; by thinking happy, positive thoughts, we are shaping our environments. And in shaping our environments, we are shaping our genetic destinies.

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Licensed Therapist offers Innovative Stress Reduction for Reducing Anxiety and Fear around COVID-19 – Yahoo Finance

Posted: April 16, 2020 at 9:43 pm

Drawing on Ancient Wisdom, Modern Science, and the field of Epigenetics.

LENOX, Mass., April 16, 2020 /PRNewswire/ -- Marc Aronoff, MA, LMHC, is delighted to announce the opening of his new Energy Healing practice, Divine-Source Healing Services, offering individual and group sessions via tele-health conference. (www.divine-sourcehealing.com). Combining traditional therapeutic modalities of Insight and Talk-therapy with ancient wisdom, a Divine-Source Healing session is a unique opportunity for stress reduction and a renewed sense of Self-confidence during difficult times.

Derived from over 30-years' experience working with individuals, groups, and Fortune 500 corporations as a Wellness Consultant, Divine-Source Healing offers tangible tools for coping more effectively with personal stress and anxiety, offering a gateway to experience deep states of relaxation and peace. This is accomplished through dialogue, inquiry, awareness, and remote healing, strengthening one's innate resources for coping in fresh new ways.

"After a divine-source healing session, I feel more relaxed in my mind and body and the feeling seems to stay as I go about my day."

Not a system of religious or dogmatic beliefs, Divine-Source Healing draws on tenets of Quantum physics and the revolutionary field of Epigenetics; which may be seen here as the genetics of our lineage. Science has shown that our state of mind and relationship to stress, in particular fear, has a profound effect on well-being and the immune system. Science also demonstrates our DNA is a "frequency generator" which is changeable: we may align with a frequency of health and healing or potentially dis-ease. The question is, in times like this, how do we care for our mental and psychic health, while isolated and faced with uncertainty. COVID-19, while demanding us to make safe choices, also offers an inner journey.

Clients often come with a range of issues from emotional distress, anxiety, and worry, to physical pain. While not a substitute for traditional medicine where needed, a Divine-Source Healing offers the chance to cultivate harmony in one's life, offering the solace of experiencing what you can do for yourself. Each 30 60-minute session is custom tailored. While these are stressful times, humans are wired for transformation. How we see and experience the world will determine our well-being. The premise is simple: We have an influence over our biology.

Contact http://www.divine-sourcehealing.com for a free consultation.

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Why Do the Identical-Looking Brain Hemispheres Act Differently? – MedicalResearch.com

Posted: April 16, 2020 at 9:43 pm

MedicalResearch.com Interview with:

Dr. Viviane Labrie, PhDDr. Labrie is an associate professor in Van Andel Institutes Center for Neurodegenerative Science, where she studies Parkinsons, Alzheimers and other neurological diseases.

MedicalResearch.com: What is the background for this study?

Response: One of the most puzzling and persistent mysteries in neuroscience has been why some people are right-brained while others are left-brained. The two sides of the brain have different jobs. The left side is analytic and problem-solving, while the right side manages creativity and artistic talents. But despite their differences, the two sides are composed of the same cell types essentially, brain neurons and their support cells. In this study, we sought to understand how it is possible for these cells to behave completely differently depending on what hemisphere theyre located in.

We also wanted to examine the reasons behind asymmetry in Parkinsons disease; that is, why Parkinsons symptoms typically start on one side of the body before the other. This asymmetry in neurodegeneration and symptoms in patients is one of the biggest unsolved puzzles in the Parkinsons disease field why do brain cells in one hemisphere begin dying before brain cells in the other hemisphere?

MedicalResearch.com: What are the main findings? What are the implications for Parkinsons disease?

Response: We found that hemispheric differences are related to molecular modifications on DNA that help determine the day job of a brain cell. Two cells that look totally identical can behave differently because of the molecular, or epigenetic, marks on the cells DNA.

Each cell in the brain has the same genes, but it is epigenetics that dictate whether those genes are switched on or off. Our team found numerous epigenetic differences between the hemispheres of healthy brains that are linked to variations in gene activity. This is important to our fundamental understanding how our brain is built and works.

It may also contribute to understanding the asymmetric nature of Parkinsons disease. In the same study, we found that asymmetry in Parkinsons disease is associated with variations in these epigenetic marks in brain neurons that affect brain development, chemical signaling and immune activation. In other words, epigenetic abnormalities on one side of the brain could make that hemisphere more susceptible to the processes that cause the death of brain cells in Parkinsons.

MedicalResearch.com: What should readers take away from your report?

Response: Both hemispheres of the brain may, at first glance, look identical in structure comprising brain neurons and their helper cells but molecular-level patterns in the cells DNA can cause vastly different behaviors in each hemisphere and enable asymmetry in the brain.

As it relates to Parkinsons disease, the brain appears to be wired at the molecular level such that one hemisphere is more vulnerable to neurogenerative processes than the other. The differences in cell death across hemispheres leads to the appearance of the diseases hallmark symptoms, such as tremors, on one side of the body before the other

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We are already looking at how the molecular differences that may cause brain asymmetry come into play in other diseases like Alzheimers, amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease), multiple sclerosis and schizophrenia.

Understanding how hemispheric differences in the brain affect disease progression sheds light on underlying factors of the disease, which has huge potential for translating into new therapeutic strategies.

Disclosures: Other authors include Peipei Li, Ph.D., Elizabeth Ensink, Sean Lang, Lee Marshall, Ph.D., and Meghan Schilthuis of Van Andel Institute; and Jared Lamp, Ph.D., and Irving Vega, Ph.D., of Michigan State University College of Human Medicine. The Flow Cytometry Core, Bioinformatics and Biostatistics Core and Pathology and Biorepository Core at Van Andel Institute and Integrated Mass Spectrometry Unit at Michigan State University also contributed to this work. Brain tissue was provided by the Parkinsons UK Brain Bank, the NIH NeuroBioBank and the Michigan Brain Bank.

This work was supported by Van Andel Institute.

Labrie is supported by the U.S. Army Medical Research Materiel Command through the Parkinsons Research Program Investigator-Initiated Research Award under award no. W81XWH1810512. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the U.S. Army. Labrie also is supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R21NS112614 and by Michigan State University through the Gibby & Friends vs. Parky Parkinsons Disease Research Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other granting organizations.

Citation:

Peipei Li, Elizabeth Ensink, Sean Lang, Lee Marshall, Meghan Schilthuis, Jared Lamp, Irving Vega, Viviane Labrie.Hemispheric asymmetry in the human brain and in Parkinsons disease is linked to divergent epigenetic patterns in neurons.Genome Biology, 2020; 21 (1) DOI:10.1186/s13059-020-01960-1

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Stem Cell therapy Gilman Vermont 05904

Posted: April 16, 2020 at 9:42 pm

Stem Cell Therapy Gilman VT 05904

Stem cell therapy has ended up being a popular argument in the worldwide medical scene. This extremely questionable treatment has actually received combined viewpoints from numerous stakeholders in the health care industry and has also attracted the interest of political leaders, spiritual leaders and the basic population at large. Stem cell therapy is thought about a revolutionary treatment for people suffering from a vast array of degenerative conditions. Some common concerns concerning this treatment are addressed below.

Are you a stem cell therapy provider in Gilman VT 05904?Contact us for more information.

Stem cells can be described as blank state or non-specialized cells that have the ability to become specialized cells in the body such as bone, muscle, nerve or organ cells. This indicates that these special cells can be utilized to regrow or develop a wide range of damaged cells and tissues in the body. Stem cell therapy is for that reason a treatment that targets at attaining tissue regrowth and can be used to cure health conditions and health problems such as osteoarthritis, degenerative disc disease, spine injury, muscular degeneration, motor nerve cell disease, ALS, Parkinsons, cardiovascular disease and a lot more.

Being a treatment that is still under studio, stem cell therapy has actually not been fully accepted as a practical treatment choice for the above pointed out health conditions and diseases. A great deal of studio is currently being carried out by scientists and medical specialists in different parts of the world to make this treatment practical and efficient. There are nevertheless different constraints enforced by federal governments on studio including embryonic stem cells.

Presently, there have not been numerous case studies carried out for this kind of treatment. Nevertheless, with the few case studies that have actually been carried out, among the significant issues that has actually been raised is the boost in a patients threat of developing cancer. Cancer is caused by the rapid multiplication of cells that tend not to die so easily. Stem cells have been associated with similar development factors that may result in formation of growths and other malignant cells in clients.

Contact us for more information about stem cell doctor in Gilman VT 05904

Stem cells can be drawn out from a young embryo after conception. These stem cells are frequently referred to as embryonic stem cells. After the stem cells are drawn out from the embryo, the embryo is terminated. This is generally among the major reasons for controversy in the field of stem cell research study. Lots of people argue that termination of an embryo is dishonest and undesirable.

New studio has however revealed pledge as researchers aim at establishing stem cells that do not form into growths in later treatment phases. These stem cells can therefore efficiently change into other types of specialized cells. This treatment is therefore worth researching into as numerous patients can gain from this innovative treatment.

Stem cells can still be acquired through other means as they can be discovered in the blood, bone marrow and umbilical cords of adult people. Normal body cells can also be reverse-engineered to become stem cells that have restricted capabilities.

stem cell therapy in Gilman VT 05904

Stem cell therapy has actually ended up being a popular dispute in the worldwide medical scene. This extremely controversial treatment has actually gotten combined viewpoints from numerous stakeholders in the health care market and has actually also attracted the interest of politicians, religious leaders and the basic population at large. Stem cell therapy is thought about an advanced treatment for individuals suffering from a wide range of degenerative conditions. Some common questions concerning this therapy are addressed below.

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Main address:Gilman, Vermont, 05904

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COBRE Center for Stem Cells and Aging | Lifespan

Posted: April 16, 2020 at 9:41 pm

TheCOBRE Center for Stem Cells and Aging grant has four projects dealing with stem cells and various aspects of aging, fibrosis and cellular senescence. The projects focus on hematopoietic stem cells, their microenvironment and the impact of aging on the fibrotic component of that microenvironment, neural stem cells, and their regulation with aging.

The renewal of our grant allows Lifespan and Rhode Island Hospital to update research infrastructure for expanded studies into normal and malignant stem cells. In turn, these upgrades in infrastructure will enhance Lifespans focus on establishing a comprehensive cancer and stem cell program that will foster the development of novel treatment strategies, conduct nationally recognized research efforts, and devise effective methods of cancer prevention

Promising applications for our research include regeneration and repair for the treatment of leukemia, lymphomas, various neurodegenerative disorders, and different aspects of aging.

COBRE Phase II aims to:

Patrycja Dubielecka, PhDMentors: Sharon Rounds, MD and Philip Gruppuso, MD

Molecular mechanisms that contribute to the pathology of myeloproliferative neoplasms at the stem cell level are not well understood. JAK/STAT cascade was found to be dysregulated in all types of myeloproliferative neoplasms essential thrombocythemia, polycythemia vera and primary myelofibrosis. However, the extent to which currently available inhibitors that target JAK/STAT pathway alter the underlying disease and affect malignant hematopoietic stem cells is not clear.

Dr. Dubieleckas long-term goal is to better understand the molecular processes responsible for malignant transformation of hematopoietic stem cells, and identify new targets for pharmacological intervention in myeloproliferative neoplasms.

The overall objective of this application is to identify new signaling mechanisms involved in the initiation of age-induced myelofibrosis and related myeloproliferative neoplasms. Her recent findings indicate that (1) conditional deletion of the gene encoding the Abelson interactor-1 (Abi-1) adapter protein in mouse bone marrow induces myelofibrotic phenotype, (2) hematopoietic progenitors and granulocytes from patients with primary myelofibrosis show decreased Abi-1 protein and transcript levels, (3) loss of Abi-1 positively affects activity of Src Family Kinases (SFKs) and their downstream signaling to STAT3 and NFkB, and finally (4) loss of Abi-1 in malignant hematopoietic stem cells leads to dysregulation of adhesion and quiescence and induces their chemo resistance.

The central hypothesis is that loss of Abi-1, through a positive effect on SFKs signaling and its downstream cross-talk with STAT3 and NF-kB, is a factor that initiates fibrosis-inducing changes at the malignant stem cell level.

Olin D. Liang, PhD

Olin D. Liang, PhDMentors: Wentian Yang, MD, PhD and James Padbury, MD

Dr. Liang is studying the role of the aged bone marrow microenvironment in normal hematopoiesis, the critical cell types for the hematopoietic niche and the role of SHIP inhibition in vivo in reconstitution of the aged and preleukemic microenvironments.

The increasing number of elderly people affected by age-related blood malignancies, mainly of the myeloid subtype, is one of the most significant public health challenges today but currently there are no effective treatments. The overall objective of this project is to investigate the role of bone marrow microenvironment in hematopoiesis and age-related leukemia. The COBRE Center for Stem Cells and Aging previously discovered that deficiency of the lipid phosphatase SHIP enables long-term reconstitution of the hematopoietic bone marrow microenvironment. This proposed study is a continuation of our prior work.

Jill A. Kreiling, PhD

Jill A. Kreiling, PhDMentors: Susan Gerbi, PhD and Eric Morrow, PhD

Dr. Kreilings research investigatesthe triggers for cellular senescence in neural stem cells, the resulting changes in chromatin structure leading to activation of retrotransposable elements and the consequences of these processes on cellular physiology.

Neurodegenerative conditions and dementias, including Alzheimers disease, create a significant economic burden and are responsible for considerable human suffering. Aging is the primary risk factor for development of these conditions. The decline in neural stem cell (NSC) function that occurs with age is a major factor contributing to the development of these conditions. However, the mechanisms resulting in NSC functional decline are poorly understood.

Recent work from Dr. Kreilings laboratory, and those of others, reveals that chromatin undergoes global remodeling with age, with an opening of heterochromatic regions and a relative closing of euchromatic regions. The highly heterochromatic regions contain large numbers of retrotransposable elements (RTEs). RTE expression also increases with age and culminates in active transposition events. Somatic transposition can lead to insertional mutagenesis and genome rearrangements creating genome instability and triggering cellular senescence.

This leads to the hypothesis: Age-associated changes in chromatin structure lead to de-repression of RTEs, resulting in DNA damage and genome instability, ultimately triggering cellular senescence and a decline in NSC function.

To test this hypothesis, Dr. Kreilings lab will perform a set of experiments designed to determine the role of increased RTE expression with age in loss of NSC function.

Ashley Webb, PhD

Ashley Webb, PhDMentors: Gilad Barnea, PhDand Richard N. Freiman PhD

The overarching goal of research in the Webb laboratory is to understand the molecular mechanisms responsible for aging and how stem cells are transformed to tumorigenic cancer stem cells. There are currently three areas of focus in the laboratory. First, the use of mouse models and genomics approaches to study the molecular mechanisms that regulate stem cell function in the mammalian brain. Second, investigation of strategies to target stem populations that cause brain cancer, called glioma stem cells. Third, a genomics approach to investigate the extent to which the mechanisms discovered in rodents are responsible for aging in humans.

Formation of new neurons from neural stem cells (NSCs) in the brain declines with age, but the mechanisms responsible remain unknown. Dr. Webbs previous work has implicated the longevity-associated transcription factor FOXO3 as a key regulator of neural stem cell homeostasis in the adult brain. The goal of this study is to uncover the underlying mechanisms primarily through FACS-based approaches.

The overall outcome of this project will be the elucidation of the changes in NSCs that occur with age, and the mechanisms responsible for the loss of NSCs in aging mice. This work will lead to important advances in our understanding of the mechanisms coordinating NSC homeostasis in the young and old brain, and may uncover to reveal novel approaches to treat cognitive decline during normal aging and neurodegenerative disease.

Comparative Molecular Evaluation of Acute Myeloid Leukemia Blasts and their Microenvironment Changes at Diagnosis and Through TherapyDiana O. Treaba, MDMentor: Peter Quesenberry, MD

Aging, fat tissue, and inflammation: translating autoimmune responses into therapeutic interventionsMarco De Cecco, PhDMentor: John Sedivy, PhD

Mesenchymal stem cell derived vesicles therapy for mitigation of acute radiation syndromesSicheng Wen, MD, PhDMentor: Peter Quesenberry, MD

Genetic and metabolic mechanisms of quiescence in stem cellsNathalie Oulhen, PhDMentor: Gary Wessel, PhD

SHP2 regulation of cartilage stem cells for articular cartilage anti-degeneration and regenerationLijun Wang, PhDMentor: Wentian Yang, MD, PhD., Douglas Moore, MS

Redefining the murine hematopoietic stem cell population in marrowLaura Goldberg, MD, PhDMentor: Peter Quesenberry, M

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COBRE Center for Stem Cells and Aging | Lifespan

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Insects are being deployed in the war against invasive species in Connecticut – Connecticut Magazine

Posted: April 16, 2020 at 9:41 pm

Claire Rutledge, associate agricultural scientist with the Connecticut Agricultural Experiment Station, shaves the bark from a young ash tree looking for emerald ash borer larvae and parasitoids.

After wandering through the forest at Cromwell Meadows Wildlife Management Area, Claire Rutledge selects a dying ash tree and goes to work.

She pulls out her drawknife a foot-long sturdy blade with handles on either end and slams it into the tree at chest height, then draws it downward until the bark can be easily peeled from the tree in long vertical strips.

As she does so, she searches for evidence of emerald ash borers, an invasive beetle from Asia that is expected to kill all of the ash trees in the Northeast in the coming decade. After peeling away several strips of bark, she reveals a series of winding tunnels like switchbacks on a hiking trail that were created by the beetles larva as it consumed the tissue between the trees bark and wood. She also points out several holes in the bark created by adult beetles as they emerged from the tree to find a mate.

But Rutledge, an entomologist with the Connecticut Agricultural Experiment Station in New Haven, and her team of seven colleagues arent just seeking evidence of the beetle. Theyre also looking for tiny parasitic wasps, offspring of a species Rutledge had released several years earlier to kill the beetles. Its a strategy called biological control, whereby the natural predators of the beetle in its native range in the Far East are released locally in an effort to keep the beetle in check.

An emerald ash borer larvae under the bark of an ash tree.

The emerald ash borer was first discovered in the U.S. in 2002 near Detroit, and it slowly expanded into ash forests in nearby states. It was found in New York in 2008 and Connecticut and Massachusetts in 2012, though it probably arrived a few years earlier. Although its rampage through the region isnt expected to end before every mature ash tree is dead, scientists like Rutledge hope that efforts to control the insect by releasing the parasitic wasps will allow future generations of the trees to fend off the invader.

The wasps use their long stinger-like ovipositor to lay their eggs through the bark and into the beetle larvae. When the wasp larvae hatch, they kill the beetle larva by eating it from the inside out.

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For a little while, the beetle larva keeps eating the tree and looks fine, but eventually it stops looking so fine and looks like a bag of Cheetos with a bunch of wasp larvae in it, says Rutledge, who has released at least one of three species of parasitic wasps at 14 sites around the state, beginning in 2013.

She measures the success of her efforts by whether the wasps are sustaining themselves in the environment and by collecting and dissecting emerald ash borer larvae to determine how many have been parasitized by the wasps. Were recovering the wasps all over the place, so they seem to be doing pretty well, she says. And 20 to 40 percent of the beetle larvae we find are killed. So we consider it a success.

A beetle species native to Asia, the emerald ash borer was first spotted in the U.S. in 2002 and in Connecticut a decade later. Their larvae live within and feed on ash trees; with no native predators, these destructive insects have proliferated in the Northeast and now threaten the entire ash tree population.

Holes and bark damage on the stump of a removed ash tree, which was damaged by the emerald ash borer

Non-native insects and plants have been invading the U.S. for more than a century, costing billions of dollars and causing significant ecological harm. Removing these invaders by conventional means the application of chemical pesticides and herbicides or manual removal of plants is a labor-intensive exercise that seldom works for long. And although biological control does not completely eliminate the problem either, practitioners say it is a self-sustaining strategy that is cost-effective and causes less harm to the environment than chemical methods.

With biocontrol, were dealing with a pest that comes from someplace else, and it left all of its natural predators behind, Rutledge says. Were trying to reintroduce them to those predators to help keep them at manageable levels.

Jian Duan (left), entomologist with the USDA Agricultural Research Service, and Claire Rutledge, associate agricultural scientist with the Connecticut Agricultural Experiment Station, look at emerald ash borer larvae under the bark of an ash tree in a study area at the Cromwell Meadows Wildlife Management Area.

Its a practice that has its origins as a means of controlling crop pests in China more than a thousand years ago. In the U.S., it was first used by the Department of Agriculture in the 1880s, and by the turn of the century it already had its first success story the eradication of an invasive insect called the cottony cushion scale that was wreaking havoc on Californias emerging citrus industry. When an Australian ladybug was released to kill the scale, it succeeded beyond all expectations. Since then, hundreds of insects have been identified to control exotic forest pests, aquatic weeds and many other invasive species.

In New England, one of the most successful biological control efforts focused on a sawfly called the birch leafminer, an insect native to Europe that was first discovered in Connecticut in 1923. The pest makes the leaves of birch trees turn brown and fall off. In the 1970s, several insects known to parasitize the leafminer in Europe were released at numerous sites from Pennsylvania to Newfoundland, and by 2007 the invader was no longer detected in the region.

Not every attempt has been as successful, however. Periodic news reports still raise the issues that resulted from hundred-year-old biocontrol efforts that have become unfortunate examples of what not to do. Most point to cane toads in Australia and mongooses in Hawaii, which were released to fight invasive pests but which became even bigger problems themselves. Similarly, several non-native parasitic insects were released to control gypsy moth caterpillars in the U.S. a century ago, but they were later found to also kill the caterpillars of numerous beneficial moths and butterflies.

The science has advanced significantly since those days, and a lot of it is with an eye toward avoiding horror stories like those, Rutledge says. We know a lot more about what works, and we do extensive testing to make sure that what we introduce is going to be specific to the host were targeting. Now we have a much better handle on things.

Or, as Rutledges colleague at the University of Massachusetts, Roy Van Driesche, says, You wouldnt judge your risk of having open heart surgery by outcomes from the 1950s, would you? Weve learned a lot since then.

The invader:Emerald ash borer, a beetle native to Asia thats killed untold numbers of ash trees in the U.S.

The defenders: Parasitic wasps, (from top)Spathius galinae, Tetrastichus planipennisi and Oobius agrili, whose larvae feast on the beetle larvae.

Today, testing of potential biological control agents is undertaken in high-security quarantine labs where years of host-specificity tests are conducted to ensure that the insect being released wont kill non-target native species. It can take up to 10 years of testing and about $1 million in research funding before scientists are convinced that an insect is safe to release. Then they must petition the U.S. Department of Agricultures Animal and Plant Health Inspection Service for a permit to release the insect.

At the quarantine lab at the University of Rhode Island, Lisa Tewksbury and a team of students are testing insects for the control of a variety of invasive plants and raising biocontrol agents for release around the region to fight pests. In collaboration with Gail Reynolds at the University of Connecticut Cooperative Extension, she is working to release a parasitic wasp known to control the lily leaf beetle, a blood-red beetle native to Asia and Europe that has killed populations of native and ornamental lilies throughout the Northeast. The beetle is no longer a serious problem in Rhode Island and eastern Massachusetts, thanks to the wasps, but control efforts in Connecticut are still underway.

The invader: Lily leaf beetle (left), aka scarlet lily beetle, indigenous to parts of Europe and Asia; feeds on the leaves, stem, buds and flowers of lilies.

The defenders: Parasitic wasps, Diaparsis jucunda (top right)andTetrastichus setifer, whose larvae feed on the beetle larvae.

According to Reynolds, the adult beetles graze on lily leaves and flowers, but the beetle larvae are more destructive, eating almost the entire plant and leaving nothing but a dead stalk. For people who love lilies, its heartbreaking, she says. Its a problem throughout Connecticut, especially for gardeners who like to grow Asiatic lilies, and its a really big problem for commercial growers. Although the beetles can be picked off by hand, thats not a practical solution for most gardeners.

Reynolds calls the parasitic wasps that control the beetles teeny tiny parasitoids you can barely see, like a tiny speck of dirt, but they can overpower the much-larger beetle. The beetle is an eye-catching red, but the larvae are not endearing because they have a fecal shield they carry all their poop on their back, she says. Theyre really disgusting.

Like the parasitic wasps that control the emerald ash borer, the wasps used against the lily leaf beetle insert their ovipositor into the larvae of the beetle to lay their eggs, and when they hatch, the wasp larvae kill the beetle larva from the inside. Then, when the wasps emerge, you have more wasps to keep the lily leaf beetle at bay, Reynolds says.

When the wasps are ready to be released, typically in May or June, Tewksbury sends them to Reynolds in a cooler via overnight mail, and Reynolds releases as many as 100 at a time at various sites around the state. Selecting those sites, however, has been more challenging than she imagined because the wasps arent an overnight success.

At first, I sent an email to garden clubs and master gardeners, and they were really interested, she says. But many people are impatient; theyre looking for a silver bullet. It takes four or five years for the wasp population to build up, and many people couldnt just sit on their hands and wait for it to happen. A lot of them sprayed pesticides or pulled their lilies out instead of waiting for the wasps to do their job.

The invader: Swallow-wort, a close relative to the milkweed plant that is toxic to the caterpillars of the struggling monarch butterflies.

The defender: Hypena opulenta moth, native to Eastern Europe and the Middle East; feeds exclusively on swallow-wort leaves.

But after finding enough people willing to give the wasps the necessary time, the wasps are spreading throughout the state and lily leaf beetle numbers are declining. The project will likely be discontinued in a year or two as biocontrol agents are approved for other pests and funding shifts to more damaging invasive species.

Next up is the release of a moth whose caterpillar feeds on swallow-wort, a European plant introduced as an ornamental by the horticulture industry that has spread into the wild. Swallow-wort is a close relative of milkweed, which monarch butterfly caterpillars feed on, but swallow-wort is toxic to monarch caterpillars.

RELATED:With a little help from their friends, monarch butterflies might soar again

Tewksbury has made test releases of the moth at the home of an entomologist in Redding who is tracking its success, and she hopes to release them this year at Bluff Point State Park in Groton, where a large area is covered in swallow-wort. The moth is already having modest success controlling the swallow-wort population in parts of southern Ontario, and releases have begun at several other Northeast states.

We release adult moths, egg laying happens soon after, and their larvae do the feeding damage on the plant, Tewksbury says. We want them to pupate and have a second generation of adults lay eggs and those larvae do some feeding damage. Then those pupate and remain in the soil and emerge next year to start the process over again. At least thats the hope.

Carole Cheah, a scientist at the Windsor office of the Connecticut Agricultural Experiment Station, raises insects to be released to kill invasive pests.

At the Windsor office of the Connecticut Agricultural Experiment Station, Carole Cheah raises poppyseed-size black ladybugs in her laboratory in an underground bunker. In dozens of clear plastic containers on shelves lining the walls are sprigs from native hemlock trees infested with a tree-killing pest from Japan called the hemlock woolly adelgid. And feeding on the pests are the nearly invisible ladybugs.

Cheah has been studying the adelgid for 26 years, beginning not long after it was first discovered in the New Haven area in the 1980s, though it first appeared in the U.S. in the 1950s at a private arboretum in Virginia. Her mentor, Mark McClure, traveled to Japan to identify the adelgids natural enemies and found a mite that he thought was promising as a biocontrol agent. In the course of studying the mite, he stumbled upon the ladybug, and Cheah was hired to investigate whether the ladybug was the adelgid predator they were looking for. It was. She has been raising and releasing them ever since.

The adelgid, an aphid-like insect that spins a white wooly cocoon around itself on the underside of hemlock needles, feeds on cells in the trees stems, which inhibits the trees ability to produce new foliage. Hemlocks throughout Connecticut except in the high elevations of the northwest part of the state were infested with the adelgid in the 1990s, but the ladybug appears to be succeeding at keeping it under control.

Beginning in 1995 at a town forest in Windsor, Cheah released about 10,000 of the ladybugs at 16 sites around the state a total of 178,000 ladybugs in an effort to quickly eradicate the adelgid.

The invader: Hemlock woolly adelgid (left), an aphid-like insect native to East Asia that feeds on hemlock and spruce trees.

The defender: Asian lady beetle (Sasajiscymnus tsugae), tiny, ladybug-like beetles that devour adelgids.

We came up with the idea of doing a high number of releases at each site, and it has really paid off, Cheah says. Our idea was to spread them around the landscape in every county of the state, and if it survived and multiplied, it would have the effect we wanted.

During a late-winter visit to Salmon River State Forest in Colchester, where 10,000 of the ladybugs were released in 2001, Cheah inspects each of the 15 trees she monitors every year and assesses their health using a variety of metrics. She stands back to look at the whole tree to estimate how much has live foliage, then stands beneath the tree and looks straight up to rate how much skylight can be seen through the foliage as a measure of foliage density.

After completing several other measurements, she approaches the next tree on her list. She grabs a low branch to look for signs of the adelgid and, with obvious satisfaction, says, no little wool balls here. At a third tree, she notes plenty of dead twigs, but she decides that the trees poor condition is more likely the result of a recent drought rather than the adelgid.

When I see a dying tree, I want to know why it died. Its not always the adelgid, Cheah says. When we started this, a lot of people said that the trees were going to die. But Ive got news for you; they dont die. Give them a chance; theyre resilient.

The next invasive pest that entomologists expect to fight using biocontrol methods is the spotted lanternfly, a planthopper native to China, India, Vietnam and eastern Asia that was first detected in Pennsylvania in 2014. It feeds by sucking the sap from the leaves, stems and trunks of more than 70 different plants, from wild and cultivated grapes to hardwood trees, vegetables and roses. It has already had a devastating impact on the wine industry in Pennsylvania. Officials in that state have been imploring residents to kill them on sight and scrape their egg masses off trees before they hatch in May. Although spotted lanternflies have not arrived in Connecticut in big numbers yet they werefirst spotted in Southbury last October staff at the Connecticut Agricultural Experiment Station expect it to eventually threaten the states agriculture industry. So scientists are already working to identify the pests native predators in China and testing them in quarantine to see if they will be successful biocontrol agents. So far, a parasitic wasp and a fungal pathogen are showing promising results.

As she returns to the parking lot at the state forest, she smiles and says, These trees are all clear. Its better than I could have hoped for. The ladybug is doing equally well elsewhere around the state, and its doing a better job of beating back the adelgid than the three or four other biocontrol agents released in other states.

Its been a success, but its not all due to biological control, she acknowledges. Its important to know the whole ecology of the tree and all the factors that influence it. We had four years of severe winters that single-handedly brought down the adelgid population by a lot.

Determining the success of most biological control efforts usually takes many years of monitoring, which can be challenging for those seeking immediate results.

Are we going to have ash trees as a component of our forest in the future? asks Claire Rutledge, staring up at a dead tree. Thats going to be a 10- to 15-year answer. We have high hopes, and things are looking good so far, but we have to be patient, and that can be really hard.

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Insects are being deployed in the war against invasive species in Connecticut - Connecticut Magazine

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Stem Cell Treatments | Stem Cell Therapies of Oklahoma …

Posted: April 14, 2020 at 2:45 am

Here at Stem Cell Therapies of Oklahoma, were firmly committed to the belief that regenerative therapy is highly beneficial. Were convinced its the answer to many soft tissue and orthopedic issues experienced by patients today. This is why weve created our cutting-edge practice to help those in pain to find relief. By adopting the latest advances in medicine, were here to help patients live their lives to the fullest.

Around 100 million people in the United States today suffer from a chronic pain condition. Sadly, many cannot find the relief they seek, even when they undergo invasive surgery. The reason for this is that treatments available today dont address the cause of the pain. This may be down to damage or dysfunction because of overuse, aging, traumatic injury or a congenital condition. Whatever the cause, traditional treatments cannot resolve it.

How Does Stem Cell Medicine Work?

The discipline of regenerative medicine covers many methods and procedures. Recently, there have been many impressive advances in the field of stem cell research. We use regenerative treatments that focus on the use of stem cells. These help the body to heal from the inside. A stem cell injection allows your body to use the cells to counteract the inflammation that damages tissues.

Regenerative medicine uses stem cells as its key component, and we have found our patients are impressed by the results. From ligament injuries and joint pain to neuropathy and autoimmune conditions, stem cell treatment could be the answer.

Who Can Benefit from Regenerative Medicine?

Stem cells and natural healing can improve the quality of life for many of our patients. However, not everyone can benefit. Every individual has his or her own healing response, and we cannot guarantee anything in the field of medicine. We will always evaluate your goals and health carefully to ensure you have the best chance of a successful outcome.

If youre keen to dramatically reduce or even eliminate your pain with no need for surgery, regenerative medicine may help. Our treatments require no downtime and there are no side effects. Our treatments also wont mask the symptoms of your condition. Instead, the stem cells will help to heal you from within so you can achieve a full recovery whenever possible. If you want to get back to a normal daily life with no pain or reduced mobility, we can help.

Contact Stem Cell Therapies of Oklahoma Today

If youre ready to find out more about our regenerative medicine treatments, contact our team today. We can offer you expert advice and answer all your questions. We help you make an informed decision about whether regenerative medicine could be the alternative pain relief solution you seek. Whatever the cause of your condition, we can advise you about whether our stem cell therapies could be beneficial. Its our mission to help you live a happier, healthier, and pain-free life.

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Stem Cell Treatments | Stem Cell Therapies of Oklahoma ...

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