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What is the Secretome? – News-Medical.net

Biological organisms are incredibly complex machines made up of innumerable parts working in complementary ways. Understanding the complex, intricate interactions between tissues and cells is, therefore, key to a holistic understanding of the organism as a whole, and over the centuries that have encompassed the science of biology many advances in scientific knowledge have been made.

Image Credit: Kateryna Kon/Shutterstock.com

One recent area of research that has been gaining prominence in the understanding of the complex inter-and-intracellular dynamics of biological organisms is the science of secretomics, a type of proteomics concerned with the study of the secretome.

The secretome as a term was coined in 2004 by Tjalsma et al. It denotes all the factors secreted by the cell, along with the constituents of the secretory pathway. The term was revised in 2010 to include specifically the proteins which are secreted into the extracellular space.

Related terms include the matrisome (the subset which includes extracellular matrix proteins and associated proteins) receptome (membrane receptors) and the adhesome (proteins involved in cell adhesion.)

Cells such as endocrines and B-lymphocytes are two classes of cells that are specifically involved in the secretion of proteins. The liver and bone marrow are major secretory organs in the human body.

In humans, secreted proteins account for between 13 and 20% of the entire proteome (the entire set of proteins expressed in an organism, cell, tissue, or genome at any given time.) Included in the secretome are such things as growth factors, coagulation factors, adhesion molecules, cytokines, proteases, and chemokines.

A significant number (36%) of the 19670-human protein-coding genes transcribe secretory proteins. Other proteins coded for by these genes are membrane-spanning, intracellular (the main type 12631 genes encode for these) and 9% have at least one secreted protein product as well as membrane-spanning products. The secretome plays a major role in cell migration, signaling, and communication.

Several methods are used by researchers to study the secretome. These include:

Image Credit: science photo/Shutterstock.com

Each method has its distinct advantages and disadvantages for studying and identifying secretory proteins. A knowledge of them is advantageous for any study using secretomics.

The growing body of research on the secretome is proving more and more important to the field of modern medical research. Many medically important secreted proteins include coagulation factors, cytokines, and growth factors and they play a myriad of physiological and pathological roles within the body.

An understanding of the secretory pathways confers knowledge of how these secretory proteins play a role in the healthy biological processes of an individual.

All cells secrete proteins to varying degrees. The study and analysis of these proteins are providing valuable sources for new drugs and therapeutics. Not only this, but a large percentage of clinical blood diagnostic tests are directed at secretory proteins.

Medically important secretory proteins include:

The secretome is still poorly understood and represents a very recent area of research in the study of intercellular pathways in the body. Secretory proteins play a role which is becoming more apparent to medical scientists as the field of secretomics evolves.

Knowledge of how the secretome functions and which pathways are specifically involved is therefore of paramount importance and will no doubt contribute to the ongoing development of novel drugs and therapeutics.

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What is the Secretome? - News-Medical.net

AVROBIO and Magenta Therapeutics Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate as a Potential Conditioning Regimen for…

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO) and Magenta Therapeutics (Nasdaq: MGTA) today announced a research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magentas novel targeted antibody-drug conjugate (ADC) for conditioning patients before they receive one of AVROBIOs investigational lentiviral gene therapies.

The collaboration will combine AVROBIOs leadership in lentiviral gene therapies with Magentas expertise in ADC-based conditioning and is expected to further the two companies shared mission to enable patients to live free from disease. Under the collaboration, AVROBIO and Magenta will jointly evaluate MGTA-117 in conjunction with one or more of AVROBIOs investigational gene therapies. Magenta will retain all commercial rights to MGTA-117. AVROBIO will retain all commercial rights to its gene therapies and will be responsible for the clinical trial costs related to the evaluation of MGTA-117 with AVROBIOs gene therapies.

This agreement with Magenta springs from our strategic focus on maintaining technology leadership in gene therapy, said Geoff MacKay, AVROBIOs president and CEO. AVROBIO has always led by investing early in technological innovations that further the field of lentiviral gene therapy, such as plato, our proprietary platform designed to optimize the safety, potency and durability of our investigational lentiviral gene therapies. Were continually assessing new technologies that could be complementary to our plato platform to sustain our cutting-edge advantage and continue to evolve platos capabilities.

We believe targeted ADCs represent the next generation of medicines to prepare patients for gene therapy or transplant in a targeted, precise way. AVROBIOs investigational gene therapies complement our platform as well as our focus and commitment to patients. This partnership will allow Magenta to validate our conditioning platform in lentiviral gene therapy applications, said Jason Gardner, D.Phil., president and chief executive officer, Magenta Therapeutics. Weve selected ADCs as the preferred modality for our conditioning programs, as we believe they offer the most promising option for more patients. We have optimized our ADCs for gene therapy and transplant settings and look forward to collaborating with AVROBIO to evaluate MGTA-117 in specific gene therapy settings. Magenta will continue to develop MGTA-117 in other diseases, including blood cancers and genetic diseases.

MGTA-117, Magentas most advanced conditioning program, is a CD117-targeted antibody engineered for the transplant setting and conjugated to amanitin, a toxin in-licensed from Heidelberg Pharma. It is designed to precisely deplete only hematopoietic stem and progenitor cells and has shown high selectivity, potent efficacy, wide safety margins and broad tolerability in non-human primate models, suggesting that it may be capable of clearing space in bone marrow to support long-term engraftment and rapid recovery in humans. Magenta plans to complete IND-enabling studies this year.

AVROBIO currently uses a personalized conditioning regimen with precision dosing of busulfan, an extensively validated conditioning agent generally considered to be the gold standard for ex vivo lentiviral gene therapy, based on decades of general use and administration to hundreds of patients treated with lentiviral gene therapy candidates. The treating clinician uses therapeutic drug monitoring (TDM) to evaluate how quickly the patient metabolizes busulfan and adjusts the dose regimen accordingly with the goal of achieving the optimum result. AVROBIO has reported early clinical data with this precision conditioning regimen with TDM in its own clinical trials, adding to a body of data that suggest busulfan can effectively clear space in the patients bone marrow, where stem cells engraft, produce generations of daughter cells carrying the therapeutic gene and make the functional protein the patient needs to maintain cellular health.

About AVROBIO

Our mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato gene therapy platform, our foundation designed to scale gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients. Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com. Follow Magenta on Twitter: @magentatx.

AVROBIO Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, the expected safety profile of our investigational gene therapies, and the potential and expected benefits of MGTA-117, Magentas investigational antibody-drug conjugate, including the ability of MGTA-117 to deplete hematopoietic stem and progenitor cells in order to clear space in bone marrow to support long-term engraftment in humans, as well as MGTA-117s potential application to AVROBIOs investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that AVROBIO may not realize the intended benefit of MGTA-117 with respect to AVROBIOs investigational gene therapies, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

Magenta Therapeutics Forward Looking Statements

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including, without limitation, statements regarding the research and clinical collaboration agreement between Magenta and AVROBIO, including the timing, progress and success of the collaboration contemplated under the agreement, the successful evaluation MGTA-117 in conjunction with one or more of AVROBIOs investigational gene therapies under the agreement, the anticipated cost allocation and other commercial terms under the agreement, Magentas strategy and business plan, as well as the future development, manufacture and commercialization between AVROBIO and Magenta. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation, risks set forth under the caption Risk Factors in Magentas most recent Annual Report on Form 10-K, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission, as well as risks, uncertainties and assumptions regarding the impact of the COVID-19 pandemic to Magentas business, operations, strategy, goals and anticipated timelines, including, without limitation, Magentas ongoing and planned preclinical activities, ability to initiate, enroll, conduct or complete ongoing and planned clinical trials, timelines for regulatory submissions and financial position. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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UB investigators uncover cellular mechanism involved in Krabbe disease – UB Now: News and views for UB faculty and staff – University at Buffalo…

A group of UB researchers have published a paper that clarifies certain cellular mechanisms that could lead to improved outcomes in patients with globoid cell leukodystrophy, commonly known as Krabbe disease.

The paper, titled Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction, was published May 5 in the journal Neuron.

The research was led by Lawrence Wrabetz and M. Laura Feltri. Wrabetz and Feltri head the Hunter James Kelly Research Institute and both are professors in the departments of Biochemistry and Neurology in the Jacobs School of Medicine and Biomedical Sciences at UB.

The institute is named for the son of former Buffalo Bills quarterback Jim Kelly. Hunter Kelly died at age 8 in 2005 from complications of Krabbe disease.

Krabbe disease is a progressive and fatal neurologic disorder that usually affects newborns and causes death before a child reaches the age of 2 or 3.

Traditionally, hematopoietic stem cell transplantation, also known as a bone marrow transplant, has improved the long-term survival and quality of life of patients with Krabbe disease, but it is not a cure.

It has long been assumed that the bone marrow transplant works by a process calledcross-correction, in which an enzyme called GALC is transferred from healthy cells to sick cells.

Using a new Krabbe disease animal model and patient samples, the UB researchers determinedthatin reality cross-correctiondoes not occur. Rather, the bone marrow transplant helps patients through a different mechanism.

The researchers first determined which cells are involved in Krabbe disease and by which mechanism. They discovered that both myelin-forming cells, or Schwann cells, and macrophages require the GALC enzyme, which is missing in Krabbe patients due to genetic mutation.

Schwann cells require GALC to prevent the formation of a toxic lipid called psychosine, which causes myelin destruction and damage to neurons. Macrophages require GALC to aid with the degradation of myelin debris produced by the disease.

The research showed that hematopoietic stem cell transplantation does not work bycross-correction, but by providing healthy macrophages with GALC.

According to Feltri, the data reveal that improvingcross-correctionwould be a way to makebone marrow transplants and other experimental therapies such as gene therapy more effective.

Bone marrow transplantation and other treatments for lysosomal storage disorders, such as enzyme replacement therapy, have historically had encouraging but limited therapeutic benefit, says study first author Nadav I. Weinstock, an MD-PhD student in the Jacobs School. Our work defined the precise cellular and mechanistic benefit of bone marrow transplantation in Krabbe disease, while also shedding light on previously unrecognized limitations of this approach.

Future studies, using genetically engineered bone marrow transplantation or other novelapproaches,may one day build on our findings and eventually bridge the gap for effectively treating patients with lysosomal disease, he continues.

UB investigators included Daesung Shin, research assistant professor at the Hunter James Kelly Research Institute; Nicholas Silvestri, clinical associate professor of neurology, Jacobs School; Narayan Dhimal, PhD student; Chelsey B. Reed, MD-PhD student; and undergraduate student Oliver Sampson.

Also participating in the research were Eric E. Irons, MD-PhD student, and Joseph T.Y. Lau, a distinguished faculty member from the Department of Molecular and Cellular Biology at Roswell Park Comprehensive Cancer Center.

The research was funded by multiple grants from the National Institutes of Health awarded to Weinstock, Shin, Wrabetz and Feltri, and also supported by Hunters Hope.

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Researchers shed new light on the structure of RNA – News-Medical.Net

Australian and US researchers have made a breakthrough in understanding the structure of a key genetic molecule, called RNA, and revealing for the first time how these changes impact RNA's function.

Publishing in the journal Nature, the research team developed a bioinformatics technique to resolve separate structures of RNA rather than viewing them as a 'blur' that averaged multiple structures. This underpinned their discovery that the structure of RNA can influence how cells function.

RNA is a DNA-like molecule that encodes genetic information. Certain viruses - including HIV and SARS-CoV2 - use RNA as their genetic material. The team were able to apply the techniques they developed to reveal how the structure of HIV's RNA genome influences which proteins the virus produces.

The international collaborative team was led by Walter and Eliza Hall Institute researcher Dr Vincent Corbin together with Mr Phil Tomezsko and Professor Silvi Rouskin at the Whitehead Institute for Biomedical Research, Boston (US). The research team also included the Institute's Computational Biology Theme Leader Professor Tony Papenfuss and mathematician and PhD student Mr Lachlan McIntosh.

At a glance

RNA is a molecule found in all living things that carries genetic information. RNA is an important regulator of how cells function, directly controlling which proteins are produced in cells, and can also switch genes on and off.

RNA molecules have a two-dimensional structure which influences how the genetic information contained within them can be accessed, said Dr Corbin, who led the project's bioinformatics research.

"The big question in RNA biology has been whether RNA molecules have a single, constant structure, or whether they can shift between different structures - and what this means for the function of a particular RNA molecule," he said.

"Our collaborators, led by Professor Silvi Rouskin, developed a technique for deciphering the structure of RNA molecules. We wanted to understand whether what we were detecting was a single structure of RNA, or an 'average' structure that blurs multiple different structures together.

"It's a bit like seeing red and yellow stripes, or blurring them together and thinking you can see orange," he said.

By developing a computational algorithm, the team were able to detect and measure the amount of different RNA structures.

We could detect these both in a test tube and in living cells, so we next looked at whether these structures influenced how RNA functioned."

Dr Vincent Corbin, Project Leader, Bioinformatics Research, Walter and Eliza Hall Institute

When RNA is produced in cells, it starts in a longer form that is 'spliced' or trimmed to remove unwanted parts.

"RNA splicing can influence how it encodes proteins," Dr Corbin said. "There are many examples of how altered RNA splicing influences how a cell functions - and in some cases, changes in RNA splicing have been associated with cancer or neurodegenerative diseases."

Certain viruses use RNA for their genome, including HIV and SARS-CoV2 (the coronavirus that causes COVID-19). In the case of HIV, RNA splicing influences which protein the virus produces - which changes at different stages of the virus's lifecycle.

"Using the HIV genome as a model system, we looked at whether RNA structure influences how HIV's RNA is spliced. We discovered that RNA structure was a critical determinant of RNA splicing in HIV, and influenced which viral proteins were produced," Dr Corbin said.

"This is the first clear evidence of how RNA structure can control RNA function. The techniques we have developed have opened up a new field of research into the role of RNA structure in regulating the function of cells."

Professor Papenfuss said the research showed how finely tuned biological systems are. "This study how very subtle changes in one tiny molecule can have big implications for the function of a virus. By using computational biology to unravel these changes, we've made a significant discovery about how viruses - and potentially human cells - function, which may underpin future discoveries about health and disease."

Source:

Journal reference:

Tomezsko, P. J., et al. (2020) Determination of RNA structural diversity and its role in HIV-1 RNA splicing. Nature. doi.org/10.1038/s41586-020-2253-5.

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University of Iowa molecular genetics researcher studying COVID-19 testing methods to alleviate test shortages – UI The Daily Iowan

Amid the COVID-19 pandemic, Val Sheffield is pivoting his research focus to find a way to test patients without using high demand cotton swabs.

University of Iowa Molecular Genetics Chair in the Carver College of Medicine Val Sheffield has made research breakthroughs in linking gene research and was recently named to a prestigious American research institutes class of 2020.

But amid the COVID-19 pandemic, Sheffield is pivoting his work to research an alternate way to test patients for novel coronavirus to alleviate a nationwide shortage of the parts in a COVID-19 test.

Sheffield and his team submitted a document April 1 to the FDA requesting emergency-use authorization to utilize a patient-sample collection method for COVID-19 testing.

My laboratory decided early on that we have the capability to help with [COVID-19] testing, Sheffield said. Testing is really important, but its behind where it should be because there arent enough official, FDA-approved swabs to collect samples from patients For the last month weve been trying to get FDA approval for our testing method where patients snort through the nose and spit into a tube, and the saliva sample is tested for the virus.

When the method is approved by the FDA, Sheffield said researchers can use it to test anyone. The most common coronavirus tests involve inserting a long cotton swab into a patients nostril. Sheffield anticipates beginning testing soon, with a limited number of patients in a study that will be the final step in getting FDA approval.

Iowa Gov. Kim Reynolds launched Test Iowa, a partnership between the state and private technology companies Domo, Qualtrics, and NomiHealth. But, the Test Iowa equipment was pending certification by the State Hygienic Lab to run tests as of Friday.

In Iowa, tests are being prioritized for those over the age of 60, with chronic health conditions, are in the hospital, or live in congregate living facilities such as a nursing home.

Iowa has tested more than 63,000 people and reported more than 10,000 cases as of Wednesday. Reynolds is using widespread testing as a signal that the state can begin the steps of reopening, seemingly going against the advice of University of Iowa researchers, who concluded that a second wave of COVID-19 cases could emerge without precautions in place.

In late April, amid his shifting work, Sheffield was elected to the 2020 class of the American Academy of Arts and Sciences.

Sheffield began as a faculty member at the UI 30 years ago and contributes to campus clinical work and research. He started as an assistant professor and has since branched out to administrative work, instruction, and research. He served as the UI Division Director of Medical Genetics for 22 years and stepped down in January to spend more time on research.

RELATED: National registrar association awards Sarah Harris with honorary membership after 30 years at UI

Sheffield has co-authored 330 peer-reviewed scientific papers, and said he has found supportive and outstanding collaborators who have been pivotal to his researchs success in his time at the UI.

My research focuses on hereditary blindness, he said. Ive worked on identifying genes that play a role in hereditary blindness. More recently, my team and I have been focusing on figuring out mechanisms by which mutations cause disease and developing treatments.

Sheffield said that his election has reinforced his obligation to serve and help others with his science. This will continue to fuel his desire to work hard and continue to further his research, Sheffield said.

David Ginsburg, James V. Neel Distinguished university professor at the University of Michigan Medical School, is also a member of the American Academy of Arts and Sciences. He first met Sheffield at the Howard Hughes Medical Institution.

Ginsburg said Sheffields research has been crucial to developing human genetic maps. Only a few academic scientists are elected to the U.S. organization a year, and Ginsburg said Sheffields election was well deserved.

Val is a fantastic physician scientist, Ginsburg said. Hes done landmark work figuring out what gene is defective for a whole variety of different, rare genetic diseases. He was one of the real pioneers tracking down these genes. He identified where the corresponding disease gene is located in our chromosomes for about 35 diseases When I was in medical school, we only knew the responsible gene for one human disease Today, we know the gene for about 6,000 human diseases, and Val was one of the early leaders in this work.

Ginsburg said he has seen how much members of the organization can grow once theyre inducted. Sheffield will be able to continue expanding his horizons in academia when he is inducted next spring, he added.

A big part of what drives what we do in academic medicine is interaction with colleagues and the new ideas that you get when meeting, talking, and interacting with colleagues in diverse fields, he said. Thats one of the greatest things the American Academy has to offer. I know it will give Val an opportunity to expand his research and intellectual contributions to the academic enterprise.

According to the American Academy of Arts and Sciences website, the 240-year-old American Academy of Arts and Sciences was founded by John Adams and John Hancock and aims to recognize scholars and leaders in various disciplines. Sheffield joins 11 other Hawkeyes already in the organization, including UI Cardiovascular Research Chair and Professor Francois Abboud.

Abboud said Sheffield, who he has known since 1990, is an internationally recognized leader in the field of human molecular genetics and genomics as well as someone he admires.

[Sheffield] is more than a great scientist, Abboud said. Ive always been impressed by his true commitment to his patients. What drives his scientific research is his extraordinary commitment to the patients. Science is his true passion. He is a brilliant scientist and an even more remarkable person.

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University of Iowa molecular genetics researcher studying COVID-19 testing methods to alleviate test shortages - UI The Daily Iowan

10 New Books We Recommend This Week – The New York Times

The great American Zen poet and eco-warrior Gary Snyder turns 90 on Friday. Ive been thinking a lot about Snyder lately, along with other nature-minded writers like Annie Dillard and Barry Lopez, as Ive grown more restless during lockdown and started spending time in the deep woods where I live. (OK, theyre not that deep. But neither was Walden Thoreau brought laundry to his mothers house! and they at least give the illusion of solitude.) Snyders no hermit. One thing I admire about his work is its sense of fellowship: how alert it is to the links between land and politics and culture. He writes about nature, sure, but also about human nature. In honor of his birthday, maybe spend a few minutes reading Axe Handles or Above Pate Valley.

Theres not much nature on this weeks list of recommended titles, but theres plenty of politics and culture. You could read Lawrence Wrights prescient new pandemic thriller, The End of October, if you dare. You say you prefer your world affairs without viruses? In that case we might suggest Dalia Sofers novel Man of My Time, about an Iranian mans path from revolutionary to government interrogator, or Gotz Alys history Europe Against the Jews, about the 19th-century political spasms that led to the Holocaust. Theres In Deep, in which David Rohde investigates the alleged existence of a bureaucratic deep state, or The Inevitability of Tragedy, in which Barry Gewen (a longtime editor at the Book Review) traces the roots of Henry Kissingers political philosophy. Or theres Nobodys Child, Susan Nordin Vinocours incisive look at the problems and promise of the insanity defense as its used in American jurisprudence.

We also recommend a Gothic novel set in the Italian Alps, a story collection about refugees and immigrants in North America, a memoiristic biography of the woman who founded Weight Watchers, and an immersion in the ways of French cooking courtesy of Bill Bufords Dirt which, come to think of it, has a lot to do with nature after all.

Gregory CowlesSenior Editor, BooksTwitter: @GregoryCowles

THE END OF OCTOBER, by Lawrence Wright. (Knopf, $27.95.) The sweeping, authoritative and genuinely intelligent thriller the sort of novel in which the author employs a bulldozer and a scalpel at the same time is a rare specimen, our critic Dwight Garner writes, and The End of October is one of those rarities. The fact that its about the world in shock and ruin because of a virus similar to Covid-19 makes it read as if its been shot out of a cannon.

MAN OF MY TIME, by Dalia Sofer. (Farrar, Straus & Giroux, $27.) Sofers second novel traces a mans path from baffled revolutionary in Iran to complicit actor in a ruthless regime sure he can undermine the system from inside. It is a master class in layering together a character who is essentially unforgivable but no less captivating. With Sofers considerable talents, the betrayals (of both self and others) that leave Hamid a brittle shell of a man are fully worthy of our intense gaze, Rebecca Makkai writes in her review.

THE ANCESTOR, by Danielle Trussoni. (Morrow/HarperCollins, $27.99.) When a genetic testing site reveals ordinary Bert Monte to be Countess Alberta Montebianco, heiress to a grand old estate in the Italian Alps, she decides to claim her birthright. Trussonis Gothic novel explores what happens next. The central contradictions in The Ancestor reside in the questions of who we are and where we belong of what divides us and what unites us, Carol Goodman writes in her review. Those are the mysteries were invited to discover in this chilling and inventive novel.

NOBODYS CHILD: A Tragedy, a Trial and a History of the Insanity Defense, by Susan Nordin Vinocour. (Norton, $28.95.) The insanity defense, deployed in fewer than 1 percent of criminal cases and successful only about a quarter of the time, nevertheless looms large in debates about crime and punishment. Vinocour shows the injustices of this sliver of our legal system meant to bring together psychiatric research and criminal law. She makes her case delicately, every page offering an incriminating new piece of evidence, scientific fact or court case that demonstrates just how unjust our legal system is to anyone suffering the misfortune of mental illness, our reviewer, Rachel Louise Snyder, writes.

THE INEVITABILITY OF TRAGEDY: Henry Kissinger and His World, by Barry Gewen. (Norton, $30.) In this magisterial account, Gewen, a longtime editor at the Book Review, traces the historical and philosophical roots of Kissingers famous realism, situating him in the context of Hannah Arendt and a cohort of other Jewish intellectuals who escaped Nazi Germany. The book is a timely and acute defense of the great realists actions, values and beliefs, according to John A. Farrells review. Gewens book is a thoughtful rumination on human behavior, philosophy and international relations,

IN DEEP: The FBI, the CIA, and the Truth About Americas Deep State, by David Rohde. (Norton, $30.) Rohde examines Donald Trumps contention that there is a deep state trying to undermine his presidency, offering a history of the conspiracy theory and concluding that, despite the presence of an institutional government made up of career civil servants, there is no such thing. Some of the books most fascinating passages trace the rise of William Barr, Trumps attorney general, from his time as a C.I.A. intern, Fred Kaplan writes in his review. Rohde highlights Barrs activism, along with a small group of other conservative lawyers, in the Federalist Society and the Catholic Information Center, which now exercise enormous influence. The tale of these groups is worth an entire book.

HOW TO PRONOUNCE KNIFE: Stories, by Souvankham Thammavongsa. (Little, Brown, $26.) Most of the characters in this spare and rigorous debut collection by Thammavongsa, a Canadian writer and poet, are immigrants in unnamed North American cities, struggling with loneliness and the challenges of mastering the English language. Thammavongsas spare, rigorous stories are preoccupied with themes of alienation and dislocation, her characters burdened by the sense of existing unseen, Sarah Resnick writes in her review. Thammavongsas gift for the gently absurd means the stories never feel dour or predictable, even when their outcomes are by some measure bleak.

THIS IS BIG: How the Founder of Weight Watchers Changed the World and Me, by Marisa Meltzer. (Little, Brown, $28.) This is a story of kinship between two women who never met: Meltzer, a journalist, and Jean Nidetch, the founder of Weight Watchers. The two have more in common than their struggles with the scale, as Meltzer frankly details. By toggling between Nidetchs story and her own, Meltzer positions herself and the weight-loss icon as battle buddies of a sort, separated by time and space, yet bound by efforts to lose weight and to thrive within the boundaries imposed on women of their respective generations, our reviewer, Lily Burana, writes. Meltzer has created a singular companionate text for those who know the agony of frustration surrounding weight as an issue, both personal and political.

EUROPE AGAINST THE JEWS: 1880-1945, by Gotz Aly. (Metropolitan/Holt, $32.99.) The origins of the Holocaust, Aly argues, are to be found in the rise of nationalism and the persecution of minorities that began in the late 19th century and solidified in the welter of new nation-states after World War I. Alys reminder of the usefulness of taking a close look at the quiet horrors of Europes interwar years feels all the more valuable today, Steven J. Zipperstein writes in his review. And his acknowledgment that comparisons between now and then once the province of the ill-informed deserve more serious attention from historians and others is just one of many reminders as to how far weve stumbled into an age of troubled sleep.

DIRT: Adventures in Lyon as a Chef in Training, Father, and Sleuth Looking for the Secret of French Cooking, by Bill Buford. (Knopf, $28.95.) Buford, whose last book was about Italian food, here delivers a delightful exploration of his immersion in French cuisine and its soul. This book may well be an even greater pleasure than its predecessor, Lisa Abend writes, reviewing it alongside two other culinary memoirs. He tangles with the btes noires of every Anglophone in France the language, the bureaucracy, the arrogance and embarks, to the great nationalistic dismay of all around him, on a quixotic investigation to prove an Italian origin theory for pot au feu and other French classics.

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10 New Books We Recommend This Week - The New York Times

Meet the ‘psychobiome’: the gut bacteria that may alter how you think, feel, and act – Science Magazine

Newly isolated bacteria grown on agar plates or their products could act as psychobiotics.

By Elizabeth PennisiMay. 7, 2020 , 9:00 AM

CAMBRIDGE, MASSACHUSETTSKatya Gavrish is searching for new brain drugs in a seemingly unlikely place: human stool samples. An earnest and focused microbiologist who trained in Russia and loves classical music, shes standing in front of a large anaerobic chamber in a lab at Holobiome, a small startup company here. She reaches into the glass-fronted chamber through Michelin Manlike sleeves to begin to dilute the sample inside. Thats the first step toward isolating and culturing bacteria that Gavrish and her Holobiome colleagues hope will produce new treatments for depression and other disorders of the brain and nervous system.

The eight-person company plans to capitalize on growing evidence from epidemiological and animal studies that link gut bacteria to conditions as diverse as autism, anxiety, and Alzheimers disease. Since its founding a mere 5 years ago, Holobiome has created one of the worlds largest collections of human gut microbes. The companys CEO, Phil Strandwitz, cannot yet say exactly what form the new treatments will take. But the targeted ailments include depression and insomnia, as well as constipation, and visceral pain like that typical of irritable bowel syndromeconditions that may have neurological as well as intestinal components. Strandwitz, a mild-mannered Midwesterner with a Ph.D. in microbiology, isnt prone to visionary statements, but neither is he short on ambition: He predicts the first human trial will start within 1 year.

The allure is simple: Drug development for neuropsychiatric disorders has lagged for decades, and many existing drugs dont work for all patients and cause unwanted side effects. A growing number of researchers see a promising alternative in microbe-based treatments, or psychobiotics, a term coined by neuropharmacologist John Cryan and psychiatrist Ted Dinan, both at University College Cork. This is a really young and really exciting field with a huge amount of potential, says Natalia Palacios, an epidemiologist at the University of Massachusetts, Lowell, who is looking into connections between gut microbes and Parkinsons disease.

Some researchers prefer a less hurried approach focused on understanding the underlying biology. But Holobiome and a few other companies are eager to cash in on the burgeoning, multibillion-dollar market that has already sprung up for other microbial therapies, which aim to treat conditions including intestinal disorders allergies, and obesity. Those companies are pushing ahead despite many unresolved questions about how psychobiotic therapies might actually work and the potential dangers of moving too fast. Theres a gold rush mentality, says Rob Knight, a microbiologist at the University of California (UC), San Diego.

Over the past 20 years, the recognition that the microbes living inside us outnumber our bodys own cells has turned our view of ourselves inside out. The gut microbiome, as its known, weighs about 2 kilogramsmore than the 1.4-kilogram human brainand may have just as much influence over our bodies. Thousands of species of microbes (not only bacteria but also viruses, fungi, and archaea) reside in the gut. And with as many as 20 million genes among them, those microbes pack a genomic punch that our measly 20,000 genes cant match. Gut bacteria can make and use nutrients and other molecules in ways the human body canta tantalizing source of new therapies.

The brain is the newest frontier, but its one with an old connection to the gut. The ancient Greeks, for example, believed mental disorders arose when the digestive tract produced too much black bile. And long before microbes were discovered, some philosophers and physicians argued that the brain and gut were partners in shaping human behavior. What probably happens is that our brain and our gut are in constant communication, says Cryan, who over the past decade has helped drive efforts to decode those communications.

Bacterial residents of the intestines may influence neurons and the brain through several routes.

V. ALTOUNIAN/SCIENCE

Epidemiological researchers have turned up intriguing connections between gut and brain disorders. For example, many people with irritable bowel syndrome are also depressed, people on the autism spectrum tend to have digestive problems, and people with Parkinsons are prone to constipation.

Researchers have also noticed an increase in depression in people taking antibioticsbut not antiviral or antifungal medications that leave gut bacteria unharmed. Last year, Jeroen Raes, a microbiologist at the Catholic University of Leuven, and colleagues analyzed the health records of two groupsone Belgian, one Dutchof more then 1000 people participating in surveys of their types of gut bacteria. People with depression had deficits of the same two bacterial species, the authors reported in April 2019 inNature Microbiology.

Researchers see ways in which gut microbes could influence the brain. Some may secrete messenger molecules that travel though the blood to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Bacterial molecules might relay signals to the vagus through recently discovered neuropod cells that sit in the lining of the gut, sensing its biochemical milieu, including microbial compounds. Each cell has a long foot that extends outward to form a synapselike connection with nearby nerve cells, including those of the vagus.

Indirect links may also exist. Increasingly, researchers see inflammation as a key factor in disorders such as depression and autism. Gut bacteria are key to proper immune system development and maintenance, and studies show that having the wrong mix of microbes can derail that process and promote inflammation. And microbial products may influence what are known as enteroendocrine cells, which reside in the lining of the gut and release hormones and other peptides. Some of those cells help regulate digestion and control insulin production, but they also release the neurotransmitter serotonin, which escapes the gut and travels throughout the body.

Finding the perfect psychobiotic requires culturing, identifying, and testing new gut microbes, work that keeps the Holobiome team busy.

Although the mechanisms remain elusive, animal studies by Cryan and others have bolstered the idea that gut microbes can influence the brain. Rats and mice given fecal transplants from people with Parkinsons, schizophrenia, autism, or depression often develop the rodent equivalents of those problems. Conversely, giving those animals fecal transplants from healthy people sometimes relieves their symptoms. The presence or absence of certain microbes in young mice affects how the mice respond to stress as adults, and other mouse studies have pointed to a role for microbes in the development of the nervous system.

At their lab, Cryan, Dinan, and their colleague Gerard Clarke think the amino acid tryptophan, which some gut bacteria produce, could be a causal link. Microbes or the bodys own cells can convert tryptophan into serotonin, a neurotransmitter implicated in depression and other psychiatric disorders. Cells also turn tryptophan into a substance called kynurenine, which reacts further to form products that can be toxic to neurons. Changes in the microbiome might tip the production of those various substances in a way that impairs mental health, Cryan says. Research has shown, for example, that people with depression convert tryptophan into kynurenine more readily than into serotonin.

Cryans group has amassed scores of papers and reviews that have helped solidify the case for microbial effects on several psychological and neurological disorders. But teasing effective fixes out of those links will be difficult, Clarke says: It is one thing to know that a particular aspect of host physiology is influenced by our gut microbes and quite another to bend this influence to our will.

Clarkes group collaborates and consults with many companies and has tested some potential psychobiotics for stress management in healthy volunteers. But he sees a long road to treatments. It will be important to understand better and more precisely the mechanisms at play.

Holobiome isnt as patient. Strandwitz founded the company in 2015 while still a graduate student in Kim Lewiss microbiology lab at Northeastern University. He very politely told me that he would join the lab only if I helped him start a company once he graduated, recalls Lewis, who is famous for discovering and working to commercialize new antibiotics from soil microbes. Lewis agreed, but he figured it would be 10 years or more before Strandwitz would have his own company. Lewis was wrong: It only took 4 years.

At Northeastern, Strandwitz learned what he calls the art of cultivation from Gavrish, who was working with Lewis on isolating soil microbes. At the time, only about 25% of gut bacteria could be grown in the lab. Gavrish, who specializes in isolating and describing new microbial species, taught Strandwitz to manipulate nutrients and use antibiotics to give slow-growing, picky bacteria a chance to survive in culture instead of being outcompeted by more aggressive species. He began to track down growth factors to keep recalcitrant species going. Now, Strandwitz says, We have in culture about 70% of the known human gut microbes. If true, its a figure few other labs can match.

One growth factor Strandwitz identified turned out to be the key to launching his entrepreneurial dreams. He and colleagues isolated a bacterium that couldnt survive on typical culture media and required an amino acid called gamma-aminobutyric acid (GABA) to thrive. GABA is a neurotransmitter that inhibits neural activity in the brain, and its misregulation has been linked to depression and other mental health problems.

The researchers reasoned that if this gut microbe had to have GABA, some other microbe must be making it. Such GABA producers might be a psychobiotic gold mine. Strandwitz and colleagues began to add gut microbes one at a time to petri dishes containing the GABA eater. If the GABA eater thrived, the scientists would know theyd found a GABA producer. They discovered such producers among three groups of bacteria, includingBactereroides. They quickly filed a patent for packaging those bacteriaor their productsto treat people with depression or other mental disorders.

At Holobiome, Stephen Skolnick tests whether bacterial cells can make GABA, an important neurotransmitter.

Before publishing those findings, the group teamed up with researchers at Weill Cornell Medicine who were doing a brain scan study of 23 people diagnosed with depression. They found that people with fewerBacteroidesbacteria had a stronger pattern of hyperactivity in the prefrontal cortex, which some researchers have associated with severe depression. The collaboration reported its findings on 10 December 2018 inNature Microbiology, along with the discovery of GABA-producing bacteria.

Holobiome further discovered that the bacteria produce GABA in the rat digestive tract, which may increase GABA levels in the brain. And it found that GABA eaters reduced learned helplessnessa symptom of depressionin those animals. One of Strandwitzs co-authors, microbial ecologist Jack Gilbert at UC San Diego, is also testing the therapeutic potential of GABA-producing bacteria in rats. His group and Holobiome have both observed that treated rats are more likely to stay longer on an uncomfortably warm surfacea test of visceral pain toleranceperhaps because elevated GABA calms them. The findings are unpublished, but theyve persuaded Gilbert to investigate whether those bacteria can also reduce anxiety in rats. Its clear they do have a neuromodulatory effect, he says.

GABA is too big to reach the brain by slipping across the blood-brain barrier, a cellular defense wall that limits the size and types of molecules that can get into the brain from blood vessels. Instead, the molecule may act through the vagus nerve or the enteroendocrine cells. Some researchers might question why bacteria would be any more beneficial than GABA-boosting drugs. But Strandwitz says the bacteria may do more than simply boost GABA. He notes that they produce molecules that may have other effects on the brain and body, thereby addressing other symptoms of depression.

He and Gilbert are unfazed by those uncertainties. If we can show an influence, without any side effects, I dont see any reason for not going forward with clinical trials, Gilbert says.

At Holobiome, Strandwitz and colleagues have identified and ranked 30 promising GABA-producing bacteria, including the ones Gilbert is testing. Now, the company is enlisting an outside manufacturer to figure out which GABA-producing bacteria are best suited to produce in large enough quantities to test in people. The researchers hope to complete regulatory and ethical reviews in time to start human trials by early 2021. Weve been able to progress at this rate because we know our microbiology, Strandwitz says. The initial target conditions are insomnia and irritable bowel syndrome with constipation.

Ultimately, Holobiome does not know whether its best products will be a single bacterial species, a group of species, or a compound made by bacteria. For now, live bugs work the best, Strandwitz says. He suggests a consortium of bacteria that includes a wider range of species than typical probiotics will be more versatile and able to treat multiple aspects of, say, depression.

Holobiome is already lookingbeyond GABA producers. Thousands of newly isolated microbes wait in frozen vials at the companys headquarters for their psychobiotic potential to be explored. Whenever we see someone publishes a new paper on the microbiome, we can check if we have those bacteria and replicate the experiments, says Holobiomes Stephen Skolnick, who recently joined the company.

A key tool for those experiments is a gut simulator, a series of flasks connected by tubing, with several portals for adding microbes and for monitoring whats happening inside. By allowing a mock microbiome to develop from different combinations of bacteria, sometimes with mammalian cells in the mix, the researchers can investigate newly isolated microbes and their products. If the scientists see promise, they can quickly pivot to thinking about additional products to develop.

Holobiomes Mariaelena Caboni examines mammalian cells used to assess how microbes affect nerve cell signaling in their hosts.

Skolnick took the lead on obtaining a patent for Holobiomes use of queuinea vitaminlike molecule only produced by certain gut microbesto improve mental well-being. The body converts queuine into building blocks for neurotransmitters such as dopamine, serotonin, and melatonin. Whether adding queuine producers or the molecule itself to the gut might help people with mental illness isnt clear, but Strandwitz says hes excited about the idea.

Its been amazing to witness the tremendous growth in the microbiome gut-brain field, says UC Los Angeles biologist Elaine Hsiao. Like Strandwitz, she is an enthusiast, having helped start two companies to develop microbial therapies for several disorders, including epilepsy and autism.

Other researchers fear entrepreneurship is outracing science. Knight says venture capitalists are funding startups developing almost any microbiome-based therapies. Some concepts are very promising and are supported by a lot of evidence, he says, but others arent, and theyre still getting money. Knight says investors see an opportunity in eager patients. (Raes says he gets almost daily emails from depressed people seeking help.)

Microbial therapies wont necessarily meet the same standards of efficacy as regular drugs. To be marketed as a pharmaceutical, a treatment has to pass muster with the U.S. Food and Drug Administration, or its equivalent in other countries, through clinical trials that prove its effectiveness against specific diseases. Most microbiome treatments so far are marketed as probiotics, for which regulatory thresholds are lower, at least in the United Statesas are limits on the health claims that a manufacturer can make. Holobiome is developing both types of products.

The field still faces considerable scientific questions, too. Besides the correlative nature of much of the research and the usual questions of whether animal studies will translate to humans, theres also the sheer complexity of the human microbiome, says Beatriz Pealver Bernab, a systems reproductive biologist at the University of Illinois, Chicago. I dont think that it will be one thing fits all. We will need to look for specific strains and dosages for different people. And, she adds, new theories and models are needed to predict how those strains will affect the individuals particular microbiome community.

Despite the obstacles, Gavrish remains confident that some strains shes growing in the anaerobic chamber will lead to treatments. After all, she says, the connection between gut microbes and the human brain has deep evolutionary roots. I truly believe you can harness the power of a million years of signaling by gut bacteria to help people.

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Meet the 'psychobiome': the gut bacteria that may alter how you think, feel, and act - Science Magazine

The Reading Quilt: ‘Does My Head Look Big in This?’ | The notebook – Philadelphia Public School Notebook

As adults may remember, the teen years are when you strive to be more like others and nothing like yourself. Individuality is social suicide. Instead, teens spend hours flooding social media with selfies that prove that they are following the adolescent social order: cloning for acceptance. Every once in a while, we hear of a teenager who bucks the system and goes rogue, risking alienation.

The yearning to be accepted and loved as an individual in spite of the magnetic pull to think like the crowd is difficult for boys, but it is especially hard for girls, who are bombarded with images depicting female perfection. Alicia Keys, the singer and songwriter, details her distress with female perfection in her new book,More Myself: A Journey. In her life, Keys wins the struggle to define herself in a world that rarely encourages a true and unique identity.

Randa Abdel-Fattahs first novel,Does My Head Look Big in This?,mirrors the concept.

Each month The Reading Quilt provides a short review of a book or play that a teacher may use to spark conversations about culture and race, along with a learning activity that may help students understand human behavior. Using the acronym QUILT, we offer readers informationabout the Quality of writing, Universal theme, and Imaginative plot, as well as a mini Lesson plan, and Talking points that stem from the books premise.

This months selection is Does My Head Look Big in This?by Randa Abdel-Fattah (2005).

Randa Abdel-Fattahwas born to Palestinian and Egyptian parents in 1979 in Sydney, Australia. She began her writing career in her late teens. While studying at the University of Melbourne, Abdel-Fattah found opportunities to write for various newspapers. Using that platform,Abdel-Fattah found the courage to hold the media responsible for their representation of Muslims. After completing her undergraduate degree, Randa continued her education, earning a Ph.D. for her studies of Islamophobia. That work laid the foundation for her writing award-winning books. Randa, who is outspoken about various issues, including womens rights, is a popular public speaker.

Quality of writing: Abdel-Fattahs book tells the story of Amal Mohamed Nasrullah Abdel-Hakim, a 16-year-old Australian Palestinian-Muslim girl who could have easily melted into the social pot without raising any eyebrows. Instead, she decides to honor her religion by wearing the hijab, a scarf that covers the head and chest and is worn by some Muslim women. Afraid that the students at McCleans Preparatory School may reject her, Amals parents arent thrilled with the idea. Despite their fears, she wears the hijab, which represents modesty, to school. Abdel-Fattahs use of natural dialogue brings to life realistic characters who spit in the face of Amals religious bravery.

Universal theme: Despite parental dismay and Islamophobia, Amal prevails in achieving self-expression and religious freedom, bringing to mind strong-willed women such as Linda Sarsour, who co-chaired the 2017 Womens March and was named one of Time magazines 100 Most Influential People that year.

Imaginative plot: Abdel-Fattah hoped to give her readers a story that debunked the common misconceptions about Muslims, which allowed readers to enter the world of the average Muslim teenage girl and see past the headlines and stereotypes, shesaid.

Lesson plan: Islamophobia, an exaggerated and illogical fear of Muslims that may incite a person to show aggression toward them, is on the rise in the United States. Students can learn why this fear has increased since the Sept. 11, 2001, attacks (also referred to as 9/11).

Talking Points:

What are some of the most significant instances of Islamophobic attacks that have occurred in the United States?

If a person said all terrorists are Muslims in your presence, how would you respond?

Do you think Muslims condemn terrorism?

Dr. Rachel Slaughter earned her doctoral degree in Cognitive Studies in Reading at Widener University. Her dissertation explores multicultural literature in private schools through the lens of Critical Pedagogy. Her new book titled Turning the Page: The Ultimate Guide for Teachers to Multicultural Literature will be published by Rowman and Littlefield in 2020. To contact her, email literacyuniversity@gmail.com. For other multicultural literary suggestions, visit literacyuniversity.org.

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The Reading Quilt: 'Does My Head Look Big in This?' | The notebook - Philadelphia Public School Notebook

The psychology of the COVID-19 coup: The elite, their victims and those who resist – NationofChange

As the elite coup against humanity continues to gather pace see The Elites COVID-19 Coup Against a Terrified Humanity: Resisting Powerfully it is invaluable to observe the way in which the dysfunctional and violent psychology of the global elite, including those of its members who have a significant public profile such as Bill Gates, is revealed more starkly.

At the same time, it is interesting to observe the vast number of fearfully submissive people who are willing to accept, or even ask for, greater constraints on our rights, freedom and economic security, ostensibly to protect them from a virus. Sadly, too, the fear of these people plays a critical collaborative role in both advancing the elite coup and condemning millions of others to death as the economic consequences of the destruction of the global economy inflicts its devastating impacts on those least able to cope with it.

Clearly complicated by a number of factors, including the locust plagues that have been devastating several countries in Africa, the Middle East and South Asia during early 2020 see 360 Billion Locusts And Growing A Plague Of Biblical Proportions Is Destroying Crops Across The Middle East And Africa but now particularly because of official responses to COVID-19, as World Food Programme (WFP) Executive Director, David Beasley, has recently warned:

If we dont prepare and act now to secure access, to avoid funding shortfalls and disruptions to trade, we could be facing multiple famines of biblical proportions within a short few months our analysis shows that 300,000 people could starve to death every single day over a three-month period. See WFP chief warns of hunger pandemic as Global Food Crises Report launched.

That is 27,000,000 people, if arithmetic is not your strong point, that will die of starvation, not COVID-19. And this figure, of course, is quite separate from the phenomenal hardship that millions are already experiencing as a result of the economic dislocation which has created s staggering number of newly unemployed people around the world.

In this article I will do three things. I will briefly explain the dysfunctional psychology of the global elite, using Bill Gates as an example, which explains why they seek vastly greater control over our lives at staggering expense to our rights, freedom and economic security. I will briefly explain why so many people are fearfully submissive victims of this coup, unable to perceive the deeper strands of what is taking place. And I will briefly reiterate what those people in a third category, ranging from those skeptical of the fear-mongering in relation to COVID-19 to those already resisting the lockdowns, curfews, martial law and other serious impositions on our lives, can do to ensure that their resistance has strategic impact.

The Violently Dysfunctional Psychology of the Global Elite

While the world is in turmoil, partly in response to the fear-mongering by WHO, governments, the medical industry and the corporate media that has profoundly inflated peoples fear of COVID-19 but also because of the adverse cascading impacts of the long list of ill-advised decisions, particularly those that impact national economies made to supposedly deal with COVID-19, the primary concern of Bill Gates is that we all submit to vaccination and acquire a digital certificate to prove that we have done so. For explanations of Gates unsavory motives in promoting and conducting extensive vaccination, see Gates Globalist Vaccine Agenda: A Win-Win for Pharma and Mandatory Vaccination and Bill Gates and the Depopulation Agenda. Robert F. Kennedy Junior Calls for an Investigation.

While this has led to substantial resistance on social media, including that Gates be arrested for crimes against humanity see Arrest Bill Gates Says every Instagrammer on Gates Account it is, in fact, only the most public initiative by a member of the global elite even though it constitutes a key element of how the global elite intends to capture complete control of our lives to create what Whitney Webb describes as a techno tyranny.

Citing a range of evidence obtained from official but largely ignored organizations, decisions and documents in recent years, Webb thoughtfully describes a frightening view of the techno tyranny that is almost upon us and for which the latest moves are being rapidly implemented under the guise of combating COVID-19. Involving an unsavory alliance of the intelligence community, the Pentagon and Silicon Valley, COVID-19 is being used as cover to remove economic and social obstacles (including so-called legacy systems with which we are all familiar) to implementing the so-called fourth industrial revolution a revolution characterized by discontinuous technological development in areas like artificial intelligence (AI), big data, fifth-generation telecommunications networking (5G), nanotechnology and biotechnology, robotics, the Internet of Things (IoT), and quantum computing to achieve everything from a cashless society and AI-driven technologies (particularly for mass surveillance and law enforcement) to driverless cars and telemedicine.

For a sample of the documentation, see Competing With China on Technology and Innovation, the US National Security Commission on Artificial Intelligence, the Chinese Tech Landscape Overview, US Attorney General William Barrs Implementation of National Disruption and Early Engagement Programs to Counter the Threat of Mass Shootings, the American Artificial Intelligence Initiative: Year One Annual Report of the US Office of Science and Technology Policy, and the recent advice by the White House that President Donald J. Trump Announces Great American Economic Revival Industry Groups. Whitney Webb has written two recent articles Meet The Companies Poised To Build The Kushner-Backed Coronavirus Surveillance System and Techno-Tyranny: How The US National Security State Is Using Coronavirus To Fulfill An Orwellian Vision and been interviewed see Security State using coronavirus to implement Orwellian nightmare that thoughtfully describe what is taking place.

In short, it will leave those of us who are still alive and who havent been replaced by robots as little more than digital entities, devoid of rights and freedoms, who are monitored and controlled to serve elite ends. You might still be able to choose what you buy, provided you do it online.

But while you can consider this evidence at your leisure, my own concern in this article is to explain why members of the global elite are so willing to inflict their violence on us, and to exploit us so mercilessly, without even caring. Why does their vision for the world and their effort to create it resemble the works of Aldous Huxley and George Orwell, rather than something that many more of us would consider desirable? Is profit really all that matters? What about people?

In short, the explanation for their behavior is that they are completely insane. But like some other versions of insanity that are also defined as normal essentially because they are so widespread (like over-consumption in industrialized countries) that few think to question whether or not the behavior is actually functional it is fairly straightforward to explain both the origin and outcomes of their insanity.

At birth, every human child has enormous unique potential. However, to fully realize that potential, the child must be nurtured physically, emotionally, intellectually and in other ways so that their unique potential unfolds. This includes caring for them in their unique physical environment while allowing their natural inclination to learn, an evolutionary gift, to guide the manner and nature of their inquiry.

Unfortunately, however, adult humans do not appreciate and value the innate learning capacities of their children so we teach them, in the ways of our choosing (particularly by funneling them all through the one-size-fits-all institution we call school), what we want them to know instead. Because the child naturally resists this, the child is subjected to an extraordinary range of visible and invisible violence to force them to conform to societal norms.

Then, using what I have labeled utterly invisible violence, we ensure that the feelings of fear, sadness, anger and pain (among many others) that this causes are suppressed so that we do not have to deal with the emotional and behavioral consequences of the violence we inflict on the child. This leaves the child with an unconscious legacy of fear, self-hatred and powerlessness that will manifest, depending on the context, throughout the childs life. For a thorough explanation of this, see Why Violence? and Fearless Psychology and Fearful Psychology: Principles and Practice.

One outcome of being terrorized into submissive obedience throughout childhood is that the human individual enters adulthood with no sense of their unique identity but fully comfortable with the social constructed delusional identity they gradually took on during childhood. Having been terrorized into obedient submission to parents, teachers and religious figures, virtually all people readily take on the role of submissive worker/soldier and citizen fulfilling some fairly meaningless role in a society largely devoid of meaning. Understanding no other way and in a last resort to feel some sense of control over their life, they also then terrorize their own children into being submissively obedient.

And people like Bill Gates are not all that different except that the opportunities provided by their wealth and the privilege that goes with it, enable them to inflict their dysfunctional and violent behaviors on a vastly greater number of people in a fruitless endeavor to feel in control. And they can do so without attracting the sanctions, legal and otherwise, that might constrain the behaviors of the rest of us.

So, as documented in the articles about Bill Gates cited above, his vaccination programs have wreaked havoc on adults and children throughout the global south, killing or incapacitating substantial numbers of people. This is unsurprising given the historical role of vaccination in precipitating a great many disorders and deaths, by introducing into the body contaminants such as aluminium and glyphosate. See Sayer Jis 326 page bibliography with a vast number of references to the literature explaining the exceptional range of shocking dangers from vaccination see Vaccination or, if you wish to just read straightforward accounts of the history of vaccine damage and the ongoing dangers, see these articles by Gary G. Kohls MD: A Comprehensive List of Vaccine-Associated Toxic Reactions and Identifying the Vaccinology-Illiterate among Us.

But does Bill Gates care about the staggering harm these vaccinations are causing? Does he care that future vaccinations are intended to be used to grotesquely infringe our rights and freedoms with the insertion of biometric data? See COVID-19: Perfect Cover for Mandatory Biometric ID. What of his love? Compassion? Empathy? Sympathy? Does he have a conscience to call him to account, even if no legal system does? Does he respect people? Does he believe everyone should be given an individual and informed choice about whether or not they are vaccinated?

Tragically, Bill Gates is so psychologically damaged that he is simply devoid of qualities such as these. They were never given the chance to develop by parents who showed him the same lack of love, sympathy, care, respect and consideration. Moreover, because of his fear of being out of control, as he was when endlessly suffering the incredible violence of his parents throughout childhood, he now endlessly seeks control in the highly dysfunctional ways that his unconscious fear projects. That is, by seeking to control us all.

If you want to read more about the psychological dysfunctionality of Bill Gates and other members of the global elite, as well as their agents, and how this always manifests to our detriment, you can do so in articles such as The Global Elite is Insane Revisited, Love Denied: The Psychology of Materialism, Violence and War and Understanding Self-Hatred in World Affairs.

Sadly, however, it is not just members of the global elite who are psychologically dysfunctional. There is a substantial portion of the human population who have suffered a similar fate, even if it manifests very differently. However, while this dysfunctionality might manifest in an extraordinarily wide variety of ways, it almost invariably includes fearful submission to those considered to be in authority.

Because each human being is unique, the individual is born with a powerful evolutionary gift: Self-will. This means that the individual has an incredible range of tools, including the capacity to apply sensory perception (sight, sound, touch) to observe what is happening, the emotional capacity to feel what this means (is it satisfying, enjoyable, frightening, infuriating), to think for themself about the significance of it, to compare and contrast it with relevant memories, to gauge it against ones conscience and so on until an integrated sense of how to behave in response is formulated and then acted on.

If a person is doing this then we might describe them as Self-aware. And they are, truly, an individual.

However, because of the experience of childhood terrorization, briefly touched on above, most children are compelled to surrender the essence of these various capacities, and hence their Self-will, by a very young age. In these circumstances, the child becomes a fairly malleable instrument, easily transformed into a victim who is now devoid of the capacity to look deep within themselves to make sound judgments about what is taking place and to behave powerfully in response.

Instead, they simply obey the will of another: parent, teacher, religious figure, employer, political leader. and act more out of habit than consideration. Given the endless violence (usually labeled punishment) that is inflicted to ensure that children are obedient to others, rather than allowed to follow their own self-will, it takes an extraordinary child to survive with even a semblance of the potential with which they were born. As a result, most human behavior lacks consideration, conviction, courage and strategy, and is simply driven compulsively by the predominant fear in each context.

For elaboration of this explanation, see The Disintegrated Mind: The Greatest Threat to Human Survival on Earth and The Psychology of Victimhood: Obama, Cameron, Netanyahu, Clinton, Kissinger.

A primary outcome of this childhood terrorization experience in materialist cultures is that the child learns to suppress their awareness of how they feel by using food and material items to distract themself. By doing this, the child rapidly loses their emerging self-awareness and learns to consume as the substitute for this awareness. Clearly, this has catastrophic consequences for the child, their society and for nature (although it is immensely profitable for elites and their agents whose Self-awareness is non-existent). For a fuller explanation, see Love Denied: The Psychology of Materialism, Violence and War.

In essence, a victim is utterly terrified and powerless. These feelings are unconscious to the victim, which is why they are incapable of intelligently seeking out and personally assessing evidence (such as that in relation to COVID-19 and how it is being used) and they simply submit without protest once told to obey.

An equally important outcome for the victim, is that they have little, if any, capacity to see beyond themselves or their immediate concerns (which might include an activist preoccupation). They are incapable of perceiving and considering the wider ramifications of what is taking place the big picture such as for those millions of starving people referred to by WFP Executive Director David Beasley above. Any sense of a wider self, of human solidarity beyond the most superficial kind, is incomprehensible to them.

So this is why a third group in relation to this elite coup is so important: Those individuals who are already resisting the coup or those who will soon choose to do so. Clearly, these people have sufficient sense of Self, the intelligence and emotional capacity (including courage) to consider the evidence in relation to COVID-19 and what lies beneath it, and to draw conclusions at variance with those presented by the elite through its international organizations (such as the World Health Organization), governments and corporate media.

And it is to these people that this final section is particularly addressed.

I have previously explained a nonviolent strategy to resist this elite coup against humanity. See The Elites COVID-19 Coup Against a Terrified Humanity: Resisting Powerfully.

This included identifying its political purpose obviously To defend humanity against a political/military coup conducted by the global elite and setting out a basic list of 26 strategic goals for achieving this purpose. You can read the Strategic goals for defeating a political/military coup conducted by the global elite against humanity by scrolling down the page at Strategic Aims.

Remaining pages on the website fully explain the twelve components of the strategy, as illustrated by the Nonviolent Strategy Wheel, as well as articles and videos explaining all of the vital points of strategy and tactics, such as those to help you understand Nonviolent Action: Why and How it Works and how to prepare, frame and conduct any nonviolent action to minimize the risk of violent repression. See Nonviolent Action: Minimizing the Risk of Violent Repression.

While many of the tactics identified are designed to make it very easy for individuals to be involved, an increasing number of people are already participating in nonviolent actions based on public gatherings to End the Lockdown using social media messaging with that or similar labels. See, for example, Protesting the Lockdowns is Getting Going #endthelockdown.

Therefore, as more people become aware of the coup and the energy to resist it continues to gather pace, it will be worthwhile to choose a locally significant date on which as many people who are willing to do so act to End the Lockdown in your country. Using a locally relevant focus, or perhaps several, for which many people would traditionally be together a cultural or sporting event, a community activity such as working to establish a community garden to increase local self-reliance, a birthday celebration and/or a return to work we can mobilize people to collectively resist the coup that is taking place.

Because the actions taken can be dispersed with large numbers of people responding in a vast number of locations, it will be impossible for police and military forces to inflict violent repression against everyone, particularly if local organizers have implemented the points in Nonviolent Action: Minimizing the Risk of Violent Repression.

Equally importantly to any of the points above, particularly given the pressing threat of human extinction see Human Extinction Now Imminent and Inevitable? A Report on the State of Planet Earth but also because becoming more self-reliant is vital to our ongoing capacity to resist elite encroachments on our rights, freedom and economic security, consider joining those participating in The Flame Tree Project to Save Life on Earth. This project also explains how to take full advantage of non-monetary forms of community where goods and services are exchanged directly, without money as a medium of exchange. Money only has value in certain types of economy and these types of economy must be superseded if humans are to survive.

Moreover, given the enormous pressure on children at the moment, as their lives are upended, it would be useful to spend time listening to them. Of course, if you know an adult who is having trouble coping, it will help them enormously as well if you listen while giving them the opportunity to talk about, and focus on feeling, their own emotional reactions to what is taking place. See Nisteling: The Art of Deep Listening. If you do not have anyone who can listen to you, try Putting Feelings First.

In addition, because the foundation of this entire elite-controlled world, and the coup it is now implementing, is the submissively obedient individual, the world can only be rebuilt as we might like it if we stop terrorizing children into being submissive. So I would start by parenting and educating children so that they become powerful. See My Promise to Children and Do We Want School or Education?

Finally, as touched on above, apart from the ongoing elite coup the Earth is under siege from our assaults on a vast range of fronts. See Human Extinction Now Imminent and Inevitable? A Report on the State of Planet Earth. So if we are serious about tackling this crisis too, we must be willing to consider committing to:

The Earth Pledge

Out of love for the Earth and all of its creatures, and my respect for their needs, from this day onwards I pledge that:

1. I will listen deeply to children (see explanation above)

2. I will not travel by plane

3. I will not travel by car

4. I will not eat meat and fish

5. I will only eat organically/biodynamically grown food

6. I will minimize the amount of fresh water I use, including by minimizing my ownership and use of electronic devices

7. I will not buy rainforest timber

8. I will not buy or use single-use plastic, such as bags, bottles, containers, cups and straws

9. I will not use banks, superannuation (pension) funds or insurance companies that provide any service to corporations involved in fossil fuels, nuclear power and/or weapons

10. I will not accept employment from, or invest in, any organization that supports or participates in the exploitation of fellow human beings or profits from killing and/or destruction of the biosphere

11. I will not get news from the corporate media (mainstream newspapers, television, radio, Google, Facebook, Twitter)

12. I will make the effort to learn a skill, such as food gardening or sewing, that makes me more self-reliant

13. I will gently encourage my family and friends to consider signing this pledge.

Conclusion

Given that any serious investigation of the circumstances underlying the so-called COVID-19 pandemic reveals that the entire global episode has been contrived to further an unsavory elite end, at staggering cost to humans everywhere, it is imperative that those who are capable of perceiving this reality also take action to bring this ongoing coup to an early end.

The longer it takes to muster a full response to defeat this coup, the more damage to our rights, freedoms, economic security, opportunities, democratic governance, the global economy and the environment will have been inflicted, making the struggle to restore them vastly more difficult.

More importantly, if human solidarity means anything to you, the lives of millions of people (in the global south) are at stake and the economic security (through lost employment) of millions more.

And these lives, if lost or marginalized, while suiting some elite depopulation agenda, will be a stark but ugly reminder that COVID-19 was never about a virus but about our fear.

FALL FUNDRAISER

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The psychology of the COVID-19 coup: The elite, their victims and those who resist - NationofChange