Date:
July 16, 2018

Source:
Lancaster University

Summary:
As the world seeks to curb human-induced climate change, will protecting the carbon of tropical forests also ensure the survival of their species? A study suggests the answer to this question is far from straightforward. Forests with the greatest carbon content do not necessarily house the most species, meaning carbon-focused conservation can miss large swathes of tropical forest biodiversity.

 

The tropical forest is home to rich biodiversity.
Credit: A. Lees

 

 

Tropical forests are rich in carbon and biodiversity. As the world seeks to curb human-induced climate change, will protecting the carbon of tropical forests also ensure the survival of their species?

A study published today in the leading journal Nature Climate Change suggests the answer to this question is far from straightforward.

Investments designed to prevent massive carbon losses from the world’s tropical forests are likely to be least effective for biodiversity in the most ecologically valuable forests, according to research by an international team, led by scientists from Lancaster University’s Environment Centre (UK) and The Brazilian Agricultural Research Corporation (EMBRAPA).

Alarmingly, in these forests, up to 77% of species that would have been protected through biodiversity conservation were not protected through measures focused solely on protecting carbon stocks.

“Securing tropical forest carbon should remain a central conservation objective,” said Dr. Gareth Lennox, co-lead author of the study and a Senior Research Associate at Lancaster University. “Not only will this slow climate change but it also has the potential to safeguard the unique and irreplaceable wildlife that inhabits these ecosystems. However, to ensure that those species survive, biodiversity needs to be treated as a priority — alongside carbon — of conservation efforts.”

The global importance of tropical forests

Tropical forests store more than a third of the world’s land carbon. When released to the atmosphere by humans, through forest disturbances — such as logging and fires — and deforestation, this carbon exacerbates global warming.

Protecting tropical forest carbon is therefore a key aim of international initiatives to blunt climate change and has attracted tens of billions of dollars of financing.

Tropical forests are also the world’s most biodiverse ecosystems, harbouring more than two-thirds of Earth’s land species, but the implications for biodiversity of investments focused only on protecting carbon stocks have until now remained unclear.

The relationship between carbon and biodiversity

The international team, comprised of scientists from Brazil, Europe and Australia, spent 18 months measuring the carbon content and species richness of plants, birds and dung beetles in 234 tropical forests in the Brazilian Amazon.

In a scientific first, they assessed carbon and biodiversity levels in forests spanning the range of human impacts, from those minimally disturbed to those recovering after complete clearance of vegetation.

Using these unprecedented data, the team found that more carbon meant more biodiversity in severely damaged forests, as anticipated. Contrary to expectations, however, where human impacts were less intense, increasing amounts of carbon did not come with more species.

Co-lead author Dr. Joice Ferreira from EMBRAPA outlined the significance of these findings: “The changing relationship between carbon and biodiversity across forests that have suffered different kinds of human disturbances explain our findings. As cleared and highly disturbed sites recover from the effects of agricultural use and severe wildfires, biodiversity also recovers. However, this linkage between carbon and biodiversity breaks down mid-recovery. The result: Forests with the greatest carbon content do not necessarily house the most species, meaning carbon-focused conservation can miss large swathes of tropical forest biodiversity.”

Focusing on both biodiversity and carbon

Alongside these more alarming findings, the study offered hope for aligning carbon and biodiversity conservation efforts. “Although trade-offs are inevitable, conflicts between carbon and biodiversity can be reduced by more integrated planning,” said Dr. Toby Gardner, Senior Research Fellow at the Stockholm Environment Institute and study co-author. “By considering carbon and biodiversity together, we found, for example, that the number of large tree species that can be protected can be increased by up to 15% relative to a carbon-only approach for just a 1% reduction in carbon coverage.”

While promising remote sensing tools are being developed to measure forest carbon, increasing biodiversity protection through carbon investments is only possible with extensive field monitoring. Yet, in Brazil, progress in this area is sorely lacking. Joice Ferreira described the situation, “As a megadiverse country, Brazil needs additional, integrated mechanisms to guarantee comprehensive monitoring of its biodiversity. Unfortunately, with government actions reducing scientific capacity and environmental protection, we are witnessing the exact opposite.”

Ultimately, curbing climate change requires the safeguarding of biodiversity. Co-author Professor Jos Barlow from Lancaster University explained why, “Biodiversity and climate change are inextricably linked in tropical forests. A warming climate and changing rainfall patterns will lead to the extinction of many tropical species, while it is within tropical biodiversity itself that forest carbon resides. Species-poor forests will eventually become carbon-poor. Therefore, tackling the climate crisis requires that both tropical forest carbon and tropical forest species are protected together.”

Story Source:

Materials provided by Lancaster UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Joice Ferreira, Gareth D. Lennox, Toby A. Gardner, James R. Thomson, Erika Berenguer, Alexander C. Lees, Ralph Mac Nally, Luiz E. O. C. Aragão, Silvio F. B. Ferraz, Julio Louzada, Nárgila G. Moura, Victor H. F. Oliveira, Renata Pardini, Ricardo R. C. Solar, Ima C. G. Vieira, Jos Barlow. Carbon-focused conservation may fail to protect the most biodiverse tropical forestsNature Climate Change, 2018; DOI: 10.1038/s41558-018-0225-7

 

Source: Lancaster University. “Protecting tropical forest carbon stocks may not prevent large-scale species loss.” ScienceDaily. ScienceDaily, 16 July 2018. <www.sciencedaily.com/releases/2018/07/180716164520.htm>.

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Date:
July 16, 2018

Source:
University of York

Summary:
A study into some of the earliest known pottery remains has suggested that the rise of ceramic production was closely linked with intensified fishing at the end of the last Ice Age.

 

This is incipient Jōmon pottery from Hanamiyama site, Yokohama-shi, Kanagawa Prefecture, Japan.
Credit: Nara National Research Institute for Cultural Properties

 

 

A study into some of the earliest known pottery remains has suggested that the rise of ceramic production was closely linked with intensified fishing at the end of the last Ice Age.

Scientists examined 800 pottery vessels in one of the largest studies ever undertaken, focussing mainly on Japan- a country recognised as being one of the earliest centres for ceramic innovation.

A three-year study led by researchers at BioArCh, the University of York, concluded that the ceramic vessels were used by our hunter-gatherer ancestors to store and process fish, initially salmon, but then a wider range including shellfish, freshwater and marine fish and mammals as fishing intensified.

Climate

Scientists say this association with fish remained stable even after the onset of climate warming, including in more southerly areas, where expanding forests provided new opportunities for hunting game and gathering plants.

The research team were able to determine the use of a range of ceramic vessels through chemical analysis of organic food compounds that remained trapped in the pots despite ca. 10,000 years of burial.

The samples analysed are some of the earliest found and date from the end of the Late Pleistocene — a time when our ancestors were living in glacial conditions — to the post-glacial period when the climate warmed close to its current temperature and when pottery began to be produced in much greater quantity.

Lipids

The study has shed new light on how prehistoric hunter-gatherers processed and consumed foods over this period — until now virtually nothing was known of how or for what early pots were used.

As part of the study, researchers recovered diagnostic lipids from the charred surface deposits of the pottery with most of the compounds deriving from the processing of freshwater or marine organisms.

Lead author, Dr Alex Lucquin, from BioArCh, Department of Archaeology, University of York, said: “Thanks to the exceptional preservation of traces of animal fat, we now know that pottery changed from a rare and special object to an every-day tool for preparing fish.

“I think that our study not only reveals the subsistence of the ancient Jōmon people of Japan but also its resilience to a dramatic change in climate.

Collaboration

Professor Oliver Craig, from the Department of Archaeology and Director of the BioArCh research centre at York, who led the study, said: “Our results demonstrate that pottery had a strong association with the processing of fish, irrespective of the ecological setting.

“Contrary to expectations, this association remained stable even after the onset of warming, including in more southerly areas, where expanding forests provided new opportunities for hunting and gathering.

“The results indicate that a broad array of fish was processed in the pottery after the end of the last Ice Age, corresponding to a period when hunter-gatherers began to settle in one place for longer periods and develop more intensive fishing strategies”

“We suggest this marks a significant change in the role of pottery of hunter-gatherers, corresponding massively with increased volume of production, greater variation in forms and sizes and the onset of shellfish exploitation.”

Dr Simon Kaner, from the University of East Anglia, who was involved in the study, added: “The research highlights the benefits of this kind of international collaboration for unlocking some of the big questions about the human past, and the potential of engaging with established research networks as created by the Sainsbury Institute over the years.”

The findings are published in Proceedings of the National Academy of Sciences and the study was funded by the AHRC. It was an international collaboration including researchers in Japan, Sweden and the Netherlands.

Story Source:

Materials provided by University of YorkNote: Content may be edited for style and length.


Journal Reference:

  1. Alexandre Lucquin, Harry K. Robson, Yvette Eley, Shinya Shoda, Dessislava Veltcheva, Kevin Gibbs, Carl P. Heron, Sven Isaksson, Yastami Nishida, Yasuhiro Taniguchi, Shōta Nakajima, Kenichi Kobayashi, Peter Jordan, Simon Kaner, Oliver E. Craig. The impact of environmental change on the use of early pottery by East Asian hunter-gatherersProceedings of the National Academy of Sciences, 2018; 201803782 DOI: 10.1073/pnas.1803782115

 

Source: University of York. “The origins of pottery linked with intensified fishing in the post-glacial period.” ScienceDaily. ScienceDaily, 16 July 2018. <www.sciencedaily.com/releases/2018/07/180716151516.htm>.

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Target Health Inc. Congratulates MDGH on Approval of Moxidectin for the Treatment of River Blindness (Onchocerciasis)

 

New York, NY – 5 July 2018: Target Health Inc. would like to congratulate Medicines Development for Global Health (MDGH) and the World Health Organisation Special Programme for Research and Training in Tropical Diseases (TDR) upon U.S. FDA approval of moxidectin 8 mg oral for the treatment of river blindness (onchocerciasis) in patients aged 12 years and older. River blindness is caused by a parasitic worm, Onchocerca volvulus. This tropical disease manifests as severe itching, disfiguring skin conditions and visual impairment, including permanent blindness caused by the worm’s larvae (microfilariae). The approval of moxidectin was based on data from two randomized, double blind, active controlled clinical studies. Each study met its respective primary endpoints, showing a statistically significant superiority of moxidectin over the current standard of care, ivermectin, in suppressing the presence of the microfilariae in skin.

 

“MDGH sincerely thanks Target Health, our US Agent and electronic submission contractor for post-NDA submission activities” said Danielle Smith, PhD, Associate Director of MDGH. Dr. Smith added that, “Target’s professionalism and expertise ensured that MDGH’ s submissions were appropriately presented for approval to the FDA, and Target Health’s flexibility was also very much appreciated as there were multiple NDA amendments, many with tight turnaround times.  Jules Mitchel,, MBA PhD, President of Target Health added that “Target Health very much looks forward to continuing our successful relationship as MDGH now heads into the post-approval phase.” MDGH US Agent and post-submission electronic submission activities at Target Health were managed by Mary Shatzoff, Sr. Director of Regulatory Affairs at Target Health.

 

The FDA awarded MDGH a priority review voucher (PRV) and full results from the Phase III study were published in the Lancet in January 2018 (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30101-6/fulltext).

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Autism and Autism Spectrum Disorder (ASD)

Toddler Stacking Cans. Repetitively stacking or lining up objects is associated with autism. Photo credit: Andwhatsnext at English Wikipedia. – Originally from en.wikipedia; description page is/was here., CC BY-SA 3.0,https://commons.wikimedia.org/w/index.php?curid=5118849

 

A toddler with autism who has arranged his toys in a row. Photo credit: Andwhatsnext at English Wikipedia. – Transferred from en.wikipedia to Commons., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1983792 

 

Autism is a developmental disorder characterized by troubles with social interaction and communication and by restricted and repetitive behavior. Parents usually notice signs in the first two or three years of their child’s life. These signs often develop gradually, though some children with autism reach their developmental milestones at a normal pace and then worsen. In the United States, a revision from autism to autism spectrum disorder (ASD) was presented in the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5), released May 2013. The new diagnosis encompasses previous diagnoses of 1) ___ disorder, Asperger syndrome, childhood disintegrative disorder, and PDD-NOS. Compared with the DSM-IV diagnosis of autistic disorder, the DSM-5 diagnosis of ASD no longer includes communication as a separate criterion and has merged social interaction and communication into one category. Slightly different diagnostic definitions are used in other countries. For example, the ICD-10 is the most commonly-used diagnostic manual in the UK and European Union. Rather than categorizing these diagnoses, the DSM-5 has adopted a dimensional approach to diagnosing disorders that fall underneath the autism spectrum umbrella. Some have proposed that individuals on the autism spectrum may be better represented as a single diagnostic category. Within this category, the DSM-5 has proposed a framework of differentiating each individual by dimensions of severity, as well as associated features (i.e., known genetic disorders, and intellectual disability). Another change to the DSM includes collapsing social and communication deficits into one domain. Thus, an individual with an ASD diagnosis will be described in terms of severity of social communication symptoms, severity of fixated or restricted behaviors or interests, and associated features. The restricting of onset age has also been loosened from 3 years of age to “early developmental period”, with a note that symptoms may manifest later when social demands exceed capabilities.

 

Autism spectrum, also known as autism spectrum 2) ___ (ASD), is a range of conditions classified as neurodevelopmental disorders. Individuals diagnosed with autism spectrum disorder present with two types of symptoms: problems in social communication and social interaction, and restricted, repetitive patterns of behavior, interests or activities. Symptoms are typically recognized between 3) ___ and two years of age. Long term issues may include difficulties in creating and keeping relationships, maintaining a job, and performing daily tasks. The cause of autism spectrum is uncertain. Risk factors include having an 4) ___ parent, a family history of the condition, and certain genetic conditions. Diagnosis is based on symptoms. The DSM-5 redefined the autism spectrum disorders to encompass the previous diagnoses of autism, Asperger syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), and childhood disintegrative disorder. Treatment efforts are generally individualized to the person’s condition. Medications may be used to try to help improve certain associated problems. Evidence to support the use of medications, however, is not very strong. Autism spectrum is estimated to affect about 1% of people (62.2 million globally as of 2015). Males are diagnosed more often than females.

 

Autism risk factors include certain infections during pregnancy, such as rubella, as well as valproic acid, alcohol or cocaine use during pregnancy. Controversies surround other proposed environmental causes, for example the vaccine hypotheses, which have been disproven. Autism affects information processing in the brain by altering how nerve cells and their 5) ___ connect and organize; how this occurs is not well understood. Early speech or behavioral interventions can help children with autism gain self-care, social skills and communication skills. Although there is no known 6) ___, there have been cases of children who have recovered from the condition. Not many children with autism live independently after reaching adulthood, though some are successful.

 

Globally, autism is estimated to affect 24.8 million people as of 2015. In the developed countries, about 1.5% of children are diagnosed with ASD as of 2017, a more than doubling from 0.7% in 2000 in the United States. It occurs four-to-five times more often in boys than girls. The number of people diagnosed has increased dramatically since the 1960s, partly due to changes in diagnostic practice; the question of whether actual rates have increased is unresolved. Overt symptoms gradually begin after the age of six months, become established by age two or three years and tend to continue through adulthood, although often in more muted form. Other aspects, such as atypical eating, are also common but are not essential for diagnosis. Individual symptoms of autism occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits.

 

Social deficits distinguish autism and the related autism spectrum disorders from other developmental disorders. People with autism have social impairments and often lack the intuition about others that many people take for granted. Noted autistic Temple Grandin described her inability to understand the social communication of neurotypicals, or people with normal neural development, as leaving her feeling “like an anthropologist on Mars.” One year after researchers published their work on a physiological test for autism, a follow-up study confirmed its exceptional success in assessing whether a child is on the autism spectrum. A physiological test that supports a clinician’s diagnostic process has the potential to lower the age at which children are diagnosed, leading to earlier treatment. Results of the study, which uses an algorithm to predict if a child has ASD based on metabolites in a 7) ___ sample, published in the June 2018 edition of Bioengineering & Translational Medicine. The study was able to predict with 88% accuracy whether children have autism. The initial success in 2017 analyzed data from a group of 149 people, about half of whom had been previously diagnosed with ASD. For each member of the group, data was obtained on 24 metabolites related to the two cellular pathways — the methionine cycle and the transsulfuration pathway. To validate the results, existing datasets were searched that included the metabolites that were analyzed in the original study. Datasets were identified that included a total of 154 children with autism. The team used their approach to recreate the predictive 8) ___, this time using data of the 22 metabolites from the original group of 149 children. The algorithm was then applied to the new group of 154 children for testing purposes. When the predictive algorithm was applied to each individual, it correctly predicted autism with 88% accuracy. This is an approach should support moving forward into 9) ___ trials and ultimately into a commercially available test. Sources: Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: A comparison and validation study. Bioengineering & Translational Medicine, 2018; DOI: 10.1002/btm2.10095; Rensselaer Polytechnic Institute. “Success of blood test for autism affirmed: First physiological test for autism proves high accuracy in second trial.” ScienceDaily.com, 19 June 2018; Wikipedia

 

Cerebrospinal fluid (CSF) may be an early marker for autism.

 

CSF is a colorless fluid that surrounds the brain and spinal cord. CSF acts as a physical buffer to protect the 10) ___from jolts. Until relatively recently, this was thought to be CSF’s only role. However, recent studies have shown that CSF also acts as a “filtration system for byproducts of brain metabolism.” As brain cells fire, they produce toxic products such as inflammatory proteins. The CSF filters out these compounds regularly, replenishing itself around four times per day. A study published in Biological Psychiatry show that levels of this fluid could potentially predict autism. The study looked at CSF and its relationship with autism. The findings showed that babies who went on to develop autism had significantly more CSF than babies who did not go on to develop the condition. Sources: Biological Psychiatry, August 2017.

 

ANSWERS: 1) autistic; 2) disorder; 3) one; 4) older; 5) synapses; 6) cure; 7) blood; 8) algorithm; 9) clinical; 10) brain

 

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Helen Rodriquez Trias MD (1929 – 2001)

Helen Rodriquez Trias MD: By National Center for Biotechnology Information – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447119/pdf/0920566.pdf, Public Domain, https://commons.wikimedia.org/w/index.php?curid=70643318

 

Helen Rodriquez Trias (July 7, 1929 – December 27, 2001) was a pediatrician, educator and women’s rights activist. She was the first Latina president of the American Public Health Association, a founding member of the Women’s Caucus of the American Public Health Association, and a recipient of the Presidential Citizens Medal. She is credited with helping to expand the range of public health services for women and children in minority and low-income populations around the world. Rodriquez Trias’s parents moved to New York City from Puerto Rico in the early part of the 20th century. After her birth, her family returned to Puerto Rico only to return to New York in 1939. In New York, Rodriquez Trias experienced racism and discrimination. In school, she was placed in a class with students who were academically handicapped, even though she had good grades and knew how to speak English. After she participated in a poem recital, her teacher realized that she was a gifted child and sent her to a class with gifted children.

 

Rodriquez Trias’s mother was a school teacher in Puerto Rico. However, in New York she was unable to get a teacher’s license. Therefore, her mother had to take in boarders to meet her financial needs and pay the rent. After Rodriquez Trias graduated from high school, she decided she would like to study medicine and that her chances would be much better in Puerto Rico because the island had a good scholarship system. In 1948, she began her academic education at the University of Puerto Rico in San Juan. The university had a very strong independence movement and Rodriquez Trias became involved with the student faction of the Puerto Rican Nationalist Party. Nationalist leader Don Pedro Albizu Campos was invited to speak by the student council; however, the chancellor of the university, Jaime Rexach Ben?tez, did not permit Albizu access to the campus. The students consequently went on strike, with Rodriquez Trias amongst them, but her brother did not approve of this. He threatened to cut off her college expenses and she returned to New York.

 

In New York, she married and had three children before she decided to return to Puerto Rico to pursue her degree. At the University of Puerto Rico, she became a student activist on issues such as freedom of speech and Puerto Rican independence. She earned her BA degree in 1957 and entered UPR’s school of medicine. She earned her medical degree in 1960 and soon after gave birth to her fourth child. During her residency at the University Hospital in San Juan, she established the first center for the care of newborn babies in Puerto Rico. The hospital’s death rate for newborns decreased 50% within three years. She established her medical practice in the field of pediatrics in the island after completing her residency. Rodriquez Trias headed the department of pediatrics at Lincoln Hospital in the South Bronx. At Lincoln Hospital, Rodriquez Trias lobbied to give all workers a voice in administrative and patient-care issues. She became involved with the Puerto Rican community and encouraged the health care workers at the hospital to become aware of the cultural issues and needs of the community. Rodriquez Trias was also an associate professor of medicine at Albert Einstein College of Medicine, Yeshiva University, and later taught at Columbia and Fordham universities.

 

During her years in Puerto Rico, Rodriquez Trias became aware that unsuspecting Puerto Rican women were being sterilized and that the United States was using Puerto Rico as a laboratory for the development of birth control technology. In 1970, she was a founding member of Committee to End Sterilization Abuse and in 1971 a founding member of the Women’s Caucus of the American Public Health Association. She supported abortion rights, fought for the abolishment of enforced sterilization, and sought neonatal care for underserved people. In 1979, she became a founding member of the Committee for Abortion Rights and Against Sterilization Abuse and testified before the Department of Health, Education, and Welfare for passage of federal sterilization guidelines. The guidelines, which she drafted, required a woman’s written consent to sterilization in a language they could understand, and set a waiting period between the consent and the sterilization procedure. She is credited with helping to expand the range of public health services for women and children in minority and low-income populations in the United States, Central and South America, Africa, Asia, and the Middle East.

 

In the 1980s, Rodriquez Trias served as medical director of the New York State Department of Health AIDS Institute. She worked on behalf of women from minority groups who were infected with HIV. In the 1990s, she served as health co-director of the Pacific Institute for Women’s Health, a nonprofit research and advocacy group dedicated to improving women’s well-being worldwide and focused on reproduction. She was a founding member of both the Women’s Caucus and the Hispanic Caucus of the American Public Health Association and the first Latina to serve as the president of the APHA.

 

On January 8, 2001, President Bill Clinton awarded Rodriquez Trias with the Presidential Citizen’s Medal, the second-highest civilian award in the United States, for her work on behalf of women, children, people with HIV and AIDS, and the poor. Later that year, on December 27, Rodriquez Trias died, a victim of cancer.

 

On July 7, 2018, which would have been Rodriquez Trias’ 89th birthday, Google featured her in a Google Doodle in the United States.

 

Presidential Citizens Medal: Photo credit: U.S. Government; Wikipedia Commons: Graphic Lab/Illustration workshop/Archive/2015

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Natural Lipid Acts as Potent Anti-Inflammatory

 

Lipids are known to help Francisella tularensis bacteria, the cause of tularemia, to suppress host inflammation when infecting mouse and human cells. Tularemia is a life-threatening disease spread to humans via contact with an infected animal or through the bite of a mosquito, tick or deer fly. Although tularemia can be successfully treated with antibiotics, it is difficult to diagnose, mainly because F. tularensis bacteria can suppress the human immune response. Dengue fever, primarily spread by Aedes aegypti mosquitoes, is rarely fatal but usually leads to a high fever, severe headache and pain throughout the body. There is no specific treatment for dengue fever.

 

According to an article published in the Journal of Innate Immunity (6 July 2018), a naturally occurring lipid has been identified that is used by F. tularensis to impair the host immune response and increase the chance of infection. Serendipitously, the authors may have also found a potent inflammation therapy against bacterial and viral diseases. The study found a form of the lipid phosphatidylethanoloamine, or PE, present in F. tularensis differs from PE found in other bacteria. In cell-culture experiments, the authos discovered that the natural and a synthetic form of PE reduced inflammation caused by both tularemia bacteria and dengue fever virus. After identifying PE as the lipid that impaired the immune response, the authors began to consider its potential therapeutic value. Because natural F. tularensis is highly infectious and therefore challenging to work with, the group developed synthetic lipids-PE2410 and PEPC2410-that would be much easier to study and produce. They then verified that both synthetic lipids also suppressed the immune response during infection of mouse and human cells in the laboratory.

 

Because several types of viral infections involve an unconstrained inflammatory response, the group tested natural and their synthetic PE in the laboratory against dengue fever virus-infected human cells. Both versions inhibited the immune response compared to the immune response seen in infected but untreated cells. Going forward, the group plans to continue exploring how F. tularensis impairs the immune response and they hope that their findings will eventually lead to the development of a potent, broad-spectrum anti-inflammatory therapeutic.

 

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Process Leading to Release of Malaria Parasites From Red Blood Cells

 

Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the Plasmodium type. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

 

The disease is most commonly transmitted by an infected female Anopheles mosquito. The mosquito bite introduces the parasites from the mosquito’s saliva into a person’s blood. The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread by humans. Most deaths are caused by P. falciparum because P. vivax, P. ovale, and P. malariae, generally cause a milder form of malaria. The species P. knowlesi rarely causes disease in humans. Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests. Methods that use the polymerase chain reaction to detect the parasite’s DNA have been developed, but are not widely used in areas where malaria is common due to their cost and complexity.

 

During a malarial infection, the vacuole, which is a compartment inside human red blood cells in which malaria parasites reproduce and develop, takes on a distinct spherical shape just minutes before its membrane ruptures, which leads to the release of parasites into the blood stream. According to an article published in Cellular Microbiology (11 July 2018), while working with red blood cells from healthy donors, the authors were able to chemically block the sequence of events leading to this rounding of the vacuole. To track the rounding sequence under a microscope, the authors dyed the membrane of the vacuole with a substance that gives off green light. About 10 minutes before the membrane ruptured, the vacuole morphed from a lumpy, uneven shape to a sphere. Previous studies have shown that malaria parasites use calcium to trigger the biochemical reactions needed for their release from the cell. When the authors treated the cells with a compound that blocks calcium’s effect, the vacuoles couldn’t transition to the spherical form, trapping the parasites inside the cell.

 

The authors noted that targeting this sequence could inform new treatment strategies against Plasmodium falciparum, the species of malaria parasite that causes the most deaths worldwide and, in several areas, has become drug-resistant.

 

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First Drug Approved to Treat Smallpox

 

Prior to its eradication in 1980, variola virus, the virus that causes smallpox, was mainly spread by direct contact between people. Symptoms typically began 10 to 14 days after infection and included fever, exhaustion, headache and backache. A rash initially consisting of small, pink bumps progressed to pus-filled sores before finally crusting over and scarring. Complications of smallpox could include encephalitis (inflammation of the brain), corneal ulcerations (an open sore on the clear, front surface of the eye) and blindness. Though the World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980, there have been longstanding concerns that smallpox could be used as a bioweapon.

 

The FDA has approved TPOXX (tecovirimat), the first drug with an indication for treatment of smallpox. TPOXX was developed in conjunction with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA).

 

TPOXX’s effectiveness against smallpox was established by studies conducted in animals infected with viruses that are closely related to the virus that causes smallpox, and was based on measuring survival at the end of the studies. More animals treated with TPOXX lived compared to the animals treated with placebo. TPOXX was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.

 

The safety of TPOXX was evaluated in 359 healthy human volunteers without a smallpox infection. The most frequently reported side effects were headache, nausea and abdominal pain. The FDA granted this application Fast Track and Priority Review designations. TPOXX also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases and a Material Threat Medical Countermeasure Priority Review Voucher, which provides additional incentives for certain medical products intended to treat or prevent harm from specific chemical, biological, radiological and nuclear threats.

 

The FDA granted approval of TPOXX to SIGA Technologies Inc.

 

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Kitchari: Adapted from Several Pakistani/Indian Recipes

Kitchari means mixture, usually of two grains. ©Joyce Hays, Target Health Inc.

 

This is a delicious vegetarian dish that stands alone or with a salad. However, you could serve it as an accompaniment with fish or poultry. ©Joyce Hays, Target Health Inc.

 

Jules and I love Kitchari. It can be varied in a multitude of ways. Here, above, is our latest meal that we shared with our son, Alex who, like us, gobbled it up. The Kitchari is served over basmati boiled in chicken broth (instead of water), with a garnish of sweet mango, yogurt and mango chutney. ©Joyce Hays, Target Health Inc.

 

Ingredients

1 cup Basmati rice or short-grained brown rice, rinsed twice

3 Tablespoons ghee or butter or extra virgin olive oil

1 inch fresh ginger, peeled then grated

4 cups stock or broth (veggie or chicken broth), extra for cooking rice and lentils

1 Tablespoon black mustard seeds, toasted

1 Tablespoon cumin seeds, toasted

1 jalapeno, seeded, chopped well

2 large carrots, roughly chopped

1 sweet potato, cubed

1 pinch kosher salt or 3 anchovy fillets mashed with 3 garlic cloves

1.5 cups yellow mung (yellow lentils) beans

1 Tablespoons turmeric

1 Tablespoon coriander powder

12 more fresh garlic cloves sliced

10 fresh garlic cloves, leave them whole

1 bunch kale, ribs removed, sliced into ribbons

1 large onion, diced

1/2 bunch cilantro, roughly chopped, plus a few sprigs for garnish

Zest of 2 fresh lemons

2 fresh lemons, juiced

Cashews, toast them in oven or in skillet on stove (optional)

Plain full-fat yogurt (optional)

Mango chutney

 

If your local store doesn’t carry some of these spices, you can probably get all of them on Amazon. ©Joyce Hays, Target Health Inc.

 

Directions

1. Follow the directions on the package of mung beans and cook now. With some, you will soak the moong beans (yellow lentils) in water for 2 hours before cooking. Cook in broth, even though the directions won’t say to do this.

2. Cook the rice in a rice cooker or in a saucepan on the stove (cook in broth: veggie or chicken broth).

3. Rinse the kale and cilantro twice and drain twice, then pat dry with paper toweling.

4. Do all your peeling, grating, toasting, mashing, chopping slicing, etc.

 

Grinding up the anchovies and garlic cloves in my mortar and pestle. This piece of equipment is not the latest fad in cooking; or mainly for gourmet chefs. In fact, it’s one of the oldest (if not THE oldest) item used in kitchens. When I use it, I’m always impressed that here in my own kitchen 21st century kitchen, we’re using the exact technology that dates back to approximately 35,000 BCE. You’ve got to have this. ©Joyce Hays, Target Health Inc.

 

Chopping and/or slicing veggies all at the same time. ©Joyce Hays, Target Health Inc.

 

5. Add two Tablespoons of butter or ghee or extra virgin olive oil, to a large pot or a Dutch oven over medium heat. Add the mustard and cumin seeds. Stir and let it sizzle for one minute, then add the jalapeno and the sliced garlic. Since I’ve made this recipe more than once, I’ve used butter, olive oil and ghee. We prefer olive oil because it’s healthier and doesn’t affect the flavor one bit.

 

Toasting the mustard and cumin seeds. Consider using a cover while you toast the seeds. When the mustard seeds start to pop, they can jump out of the pan. You don’t want to get hit in the face or eye. ©Joyce Hays, Target Health Inc.

 

Seeds are done, so slowly adding more, stirring everything together. ©Joyce Hays, Target Health Inc.

 

6. Add the carrots, sweet potato and anchovy/garlic, to the pot, and saut? for three minutes.

 

Adding the carrots and sweet potatoes. ©Joyce Hays, Target Health Inc.

 

7. Add the yellow mung beans, turmeric and coriander. Stir and cook for approximately one minute.

 

Adding the mung (yellow lentils) beans and spices. ©Joyce Hays, Target Health Inc.

 

8. To the pot, add four cups of broth. Bring to a boil, lower to a simmer and cover. Add the whole garlic cloves and stir in. Cook for 20 minutes, or until the sweet potatoes and carrots are cooked through and the mung beans have fallen apart.

 

Broth has been added, plus garlic. Now, will cover and cook for 20 minutes. ©Joyce Hays, Target Health Inc.

 

9. Toss the kale in the pot and simmer for 10 more minutes with the lid on.

 

Adding the kale. Notice how much thicker the rest of the stew has become in the 20 minutes of cooking. ©Joyce Hays, Target Health Inc.

 

10. While the kale is cooking, grab a small saut? pan and heat the remaining Tablespoon of olive oil, or butter or ghee. Add the onions and saut? until deep, golden brown. Throw in the cilantro and stir.

11. Transfer the onions and cilantro (plus any juices) from the pan to the pot and stir to combine.

12. Let the stew simmer for five minutes, then add the lemon juice and stir to combine. If you’re using the cashews, add them now and stir into the Kitchari. Remove the pot from heat and let stand for a few minutes.

 

Simmering. Just about ready to serve. ©Joyce Hays, Target Health Inc.

 

When ready to serve, add 1 or 2 Tablespoons of cooked brown or white rice to a soup bowl or plate, and add 2 or 3 Tablespoons of kitchari on top of the rice. Next to the kitchari, add some plain yogurt and garnish with a few sprigs of fresh cilantro.

 

Have Mango chutney on the table and extra yogurt

 

Read more

 

Here is the first delicious Kitchari meal: Kitchari over basmati plus some veggies roasted on a baking sheet with olive oil drizzled over the veggies. We love Kitchari and plan to have it often. The next morning, I weighed less. ©Joyce Hays, Target Health Inc.

 

At another meal, we had Kitchari over saffron rice, roasted veggies and chicken thighs. ©Joyce Hays, Target Health Inc.

 

We started this meal with icy Pouilly-Fuisse in chilled glasses, warm pita bread and garlic hummus. Next came the Kitchari with basmati rice, yogurt and mango chutney (we didn’t add cashews). For dessert, (see above) fresh red seedless grapes and vanilla Tofutti (soy) ice cream. We felt happy and healthy and knew that when we got on the bathroom scales the next morning, we’d still be happy. ©Joyce Hays, Target Health Inc.

 

This icy white wine in pre-chilled glasses, was a good pairing for the Kitchari.  ©Joyce Hays, Target Health Inc.

 

If you’re not familiar with Pakistani or Indian food, you’re in for a real flavor treat in which you can adjust the spiciness to suit your taste. My first experience was when I was living in London, having dinner at a restaurant with friends, I could not believe how hot my mouth got. I ended up drinking a whole pitcher of ice water, before I felt like myself again. You do not need to go through that, if you’re doing the cooking. Most restaurants now ask if you want your order hot, medium spicy, mild or very mild. In your own kitchen, you customize all recipes.

 

In my early twenties, when I was doing a lot of yoga and living in Manhattan, I was also well acquainted with Swami Satchidananda (we called him Swamiji), where I attended his many lectures and often spent time in his kitchen, with others like Peter Max, where he taught me how to make curried cauliflower with potato. We became such good friends, that we invited him to come for a long weekend to our summer place in the Adirondacks, on the shores of a large lake. At the time I was driving a diesel Mercedes with a stick shift. He loved to drive it with his left leg in the lotus position and the other leg in driving position. When we went sailing, he would stand on the bow, gripping the mast, like a living figurehead, his saffron robes whipping in the wind. He was really something to behold; a very special person.

 

Swami Satchidananda (aka Swamiji

 

Have a great week everyone!

Bon Appetit!

 

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With faster, cheaper, more precise technique, authors say it’s ‘off to the races’ toward new cell therapies

Date:
July 11, 2018

Source:
University of California – San Francisco

Summary:
In an achievement that has significant implications for research, medicine, and industry, scientists have genetically reprogrammed the human immune cells known as T cells without using viruses to insert DNA. The researchers said they expect their technique — a rapid, versatile, and economical approach employing CRISPR gene-editing technology — to be widely adopted in the burgeoning field of cell therapy, accelerating the development of new and safer treatments for cancer, autoimmunity, and other diseases, including rare inherited disorders.

 

The research team created CRISPR guides that would cause green fluorescent protein to be expressed in only certain cellular locations and structures.
Credit: Alex Marson’s Lab.

 

 

In an achievement that has significant implications for research, medicine, and industry, UC San Francisco scientists have genetically reprogrammed the human immune cells known as T cells without using viruses to insert DNA. The researchers said they expect their technique — a rapid, versatile, and economical approach employing CRISPR gene-editing technology — to be widely adopted in the burgeoning field of cell therapy, accelerating the development of new and safer treatments for cancer, autoimmunity, and other diseases, including rare inherited disorders.

The new method, described in the July 11, 2018 issue of Nature, offers a robust molecular “cut and paste” system to rewrite genome sequences in human T cells. It relies on electroporation, a process in which an electrical field is applied to cells to make their membranes temporarily more permeable. After experimenting with thousands of variables over the course of a year, the UCSF researchers found that when certain quantities of T cells, DNA, and the CRISPR “scissors” are mixed together and then exposed to an appropriate electrical field, the T cells will take in these elements and integrate specified genetic sequences precisely at the site of a CRISPR-programmed cut in the genome.

“This is a rapid, flexible method that can be used to alter, enhance, and reprogram T cells so we can give them the specificity we want to destroy cancer, recognize infections, or tamp down the excessive immune response seen in autoimmune disease,” said UCSF’s Alex Marson, MD, PhD, associate professor of microbiology and immunology, member of the UCSF Helen Diller Family Comprehensive Cancer Center, and senior author of the new study. “Now we’re off to the races on all these fronts.”

But just as important as the new technique’s speed and ease of use, said Marson, also scientific director of biomedicine at the Innovative Genomics Institute, is that the approach makes it possible to insert substantial stretches of DNA into T cells, which can endow the cells with powerful new properties. Members of Marson’s lab have had some success using electroporation and CRISPR to insert bits of genetic material into T cells, but until now, numerous attempts by many researchers to place long sequences of DNA into T cells had caused the cells to die, leading most to believe that large DNA sequences are excessively toxic to T cells.

To demonstrate the new method’s versatility and power, the researchers used it to repair a disease-causing genetic mutation in T cells from children with a rare genetic form of autoimmunity, and also created customized T cells to seek out and kill human melanoma cells.

Viruses cause infections by injecting their own genetic material through cell membranes, and since the 1970s scientists have exploited this capability, stripping viruses of infectious features and using the resulting “viral vectors” to transport DNA into cells for research, gene therapy, and in a well-publicized recent example, to create the CAR-T cells used in cancer immunotherapy.

T cells engineered with viruses are now approved by the U.S. Food and Drug Administration to combat certain types of leukemia and lymphoma. But creating viral vectors is a painstaking, expensive process, and a shortage of clinical-grade vectors has led to a manufacturing bottleneck for both gene therapies and cell-based therapies. Even when available, viral vectors are far from ideal, because they insert genes haphazardly into cellular genomes, which can damage existing healthy genes or leave newly introduced genes ungoverned by the regulatory mechanisms which ensure that cells function normally. These limitations, which could potentially lead to serious side effects, have been cause for concern in both gene therapy and cell therapies such as CAR-T-based immunotherapy.

“There has been thirty years of work trying to get new genes into T cells,” said first author Theo Roth, a student pursuing MD and PhD degrees in UCSF’s Medical Scientist Training Program who designed and led the new study in Marson’s lab. “Now there should no longer be a need to have six or seven people in a lab working with viruses just to engineer T cells, and if we begin to see hundreds of labs engineering these cells instead of just a few, and working with increasingly more complex DNA sequences, we’ll be trying so many more possibilities that it will significantly speed up the development of future generations of cell therapy.”

After nearly a year of trial-and-error, Roth determined the ratios of T cell populations, DNA quantity, and CRISPR abundance that, combined with an electrical field delivered with the proper parameters, would result in efficient and accurate editing of the T cells’ genomes.

To validate these findings, Roth directed CRISPR to label an array of different T cell proteins with green fluorescent protein (GFP), and the outcome was highly specific, with very low levels of “off-target” effects: each subcellular structure Roth’s CRISPR templates had been designed to tag with GFP — and no others — glowed green under the microscope.

Then, in complementary experiments devised to serve as proof-of-principle of the new technique’s therapeutic promise, Roth, Marson, and colleagues showed how it could potentially be used to marshal T cells against either autoimmune disease or cancer.

In the first example, Roth and colleagues used T cells provided to the Marson lab by Yale School of Medicine’s Kevan Herold, MD. The cells came from three siblings with a rare, severe autoimmune disease that has so far been resistant to treatment. Genomic sequencing had shown that the T cells in these children carry mutations in a gene called IL2RA. This gene contains instructions for a cell-surface receptor essential for the development of regulatory T cells, or Tregs, which keep other immune cells in check and prevent autoimmunity.

With the non-viral CRISPR technique, the UCSF team was able to quickly repair the IL2RA defect in the children’s T cells, and to restore cellular signals that had been impaired by the mutations. In CAR-T therapy, T cells that have been removed from the body are engineered to enhance their cancer-fighting ability, and then returned to the body to target tumors. The researchers hope that a similar approach could be effective for treating autoimmune diseases in which Tregs malfunction, such as that seen in the three children with the IL2RA mutations.

In a second set of experiments conducted in collaboration with Cristina Puig-Saus, PhD, and Antoni Ribas, MD, of the Parker Institute for Cancer Immunotherapy at UCLA, the scientists completely replaced native T cell receptors in a population of normal human T cells with new receptors that had been specifically engineered to seek out a particular subtype of human melanoma cells. T cell receptors are the sensors the cells use to detect disease or infection, and in lab dishes the engineered cells efficiently homed in on the targeted melanoma cells while ignoring other cells, exhibiting the sort of specificity that is a major goal of precision cancer medicine.

Without using viruses, the researchers were able to generate large numbers of CRISPR-engineered cells reprogrammed to display the new T cell receptor. When transferred into mice implanted with human melanoma tumors, the engineered human T cells went to the tumor site and showed anti-cancer activity.

“This strategy of replacing the T cell receptor can be generalized to any T cell receptor,” said Marson, also a member of the Parker Institute for Cancer Immunotherapy at UCSF and a Chan Zuckerberg Biohub Investigator. “With this new technique we can cut and paste into a specified place, rewriting a specific page in the genome sequence.”

Roth said that because the new technique makes it possible to create viable custom T cell lines in a little over a week, it has already transformed the research environment in Marson’s lab. Ideas for experiments that were previously deemed too difficult or expensive because of the obstacles presented by viral vectors are now ripe for investigation. “We’ll work on 20 ‘crazy’ ideas,” Roth said, “because we can create CRISPR templates very rapidly, and as soon as we have a template we can get it into T cells and grow them up quickly.”

Marson attributes the new method’s success to Roth’s “absolute perseverance” in the face of the widespread beliefs that viral vectors were necessary and that only small pieces of DNA could be tolerated by T cells. “Theo was convinced that if we could figure out the right conditions we could overcome these perceived limitations, and he put in a Herculean effort to test thousands of different conditions: the ratio of the CRISPR to the DNA; different ways of culturing the cells; different electrical currents. By optimizing each of these parameters and putting the best conditions together he was able to see this astounding result.”

Story Source:

Materials provided by University of California – San Francisco. Original written by Pete Farley. Note: Content may be edited for style and length.


Journal Reference:

  1. Theodore L. Roth, Cristina Puig-Saus, Ruby Yu, Eric Shifrut, Julia Carnevale, P. Jonathan Li, Joseph Hiatt, Justin Saco, Paige Krystofinski, Han Li, Victoria Tobin, David N. Nguyen, Michael R. Lee, Amy L. Putnam, Andrea L. Ferris, Jeff W. Chen, Jean-Nicolas Schickel, Laurence Pellerin, David Carmody, Gorka Alkorta-Aranburu, Daniela del Gaudio, Hiroyuki Matsumoto, Montse Morell, Ying Mao, Min Cho, Rolen M. Quadros, Channabasavaiah B. Gurumurthy, Baz Smith, Michael Haugwitz, Stephen H. Hughes, Jonathan S. Weissman, Kathrin Schumann, Jonathan H. Esensten, Andrew P. May, Alan Ashworth, Gary M. Kupfer, Siri Atma W. Greeley, Rosa Bacchetta, Eric Meffre, Maria Grazia Roncarolo, Neil Romberg, Kevan C. Herold, Antoni Ribas, Manuel D. Leonetti, Alexander Marson. Reprogramming human T cell function and specificity with non-viral genome targetingNature, 2018; DOI: 10.1038/s41586-018-0326-5

 

Source: University of California – San Francisco. “T cell engineering breakthrough sidesteps need for viruses in gene-editing: With faster, cheaper, more precise technique, authors say it’s ‘off to the races’ toward new cell therapies.” ScienceDaily. ScienceDaily, 11 July 2018. <www.sciencedaily.com/releases/2018/07/180711131204.htm>.

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