1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
<>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
<>
1d
1d
The idea for gene therapy—a type of DNA-based medicine that inserts a healthy gene into cells to replace a mutated, disease-causing variant—was first published in 1972. After decades of disputed results, treatment failures and some deaths in experimental trials, the first gene therapy drug, for a type of skin cancer, was approved in China in 2003. The rest of the world was not easily convinced of the benefits, however, and it was not until 2017 that the U.S. approved one of these medicines. Since then, the pace of approvals has accelerated quickly. At least nine gene therapies have been approved for certain kinds of cancer, some viral infections and a few inherited disorders. A related drug type interferes with faulty genes by using stretches of DNA or RNA to hinder their workings. After nearly half a century, the concept of genetic medicine has become a reality.
GENE INSERTION
These treatments use a harmless virus to carry a good gene into cells, where the virus inserts it into the existing genome, canceling the effects of harmful mutations in another gene.
GENDICINE: China's regulatory agency approved the world's first commercially available gene therapy in 2003 to treat head and neck squamous cell carcinoma, a form of skin cancer. Gendicine is a virus engineered to carry a gene that has instructions for making a tumor-fighting protein. The virus introduces the gene into tumor cells, causing them to increase the expression of tumor-suppressing genes and immune response factors.The drug is still awaiting FDA approval.
GLYBERA: The first gene therapy to be approved in the European Union treated lipoprotein lipase deficiency (LPLD), a rare inherited disorder that can cause severe pancreatitis. The drug inserted the gene for lipoprotein lipase into muscle cells. But because LPLD occurs in so few patients, the drug was unprofitable. By 2017 its manufacturer declined to renew its marketing authorization; Glybera is no longer on the market.
Turning DNA into Drugs
IMLYGIC: The drug was approved in China, the U.S. and the E.U. to treat melanoma in patients who have recurring skin lesions following initial surgery. Imlygic is a modified genetic therapy inserted directly into tumors with a viral vector, where the gene replicates and produces a protein that stimulates an immune response to kill cancer cells.
KYMRIAH: Developed for patients with B cell lymphoblastic leukemia, a type of cancer that affects white blood cells in children and young adults, Kymriah was approved by the FDA in 2017 and the E.U. in 2018. It works by introducing a new gene into a patient's own T cells that enables them to find and kill cancer cells.
LUXTURNA: The drug was approved by the FDA in 2017 and in the E.U. in 2018 to treat patients with a rare form of inherited blindness called biallelic RPE65 mutation-associated retinal dystrophy. The disease affects between 1,000 and 2,000 patients in the U.S. who have a mutation in both copies of a particular gene, RPE65. Luxturna delivers a normal copy of RPE65 to patients' retinal cells, allowing them to make a protein necessary for converting light to electrical signals and restoring their vision.
STRIMVELIS: About 15 patients are diagnosed in Europe every year with severe immunodeficiency from a rare inherited condition called adenosine deaminase deficiency (ADA-SCID). These patients' bodies cannot make the ADA enzyme, which is vital for healthy white blood cells. Strimvelis, approved in the E.U. in 2016, works by introducing the gene responsible for producing ADA into stem cells taken from the patient's own marrow. The cells are then reintroduced into the patient's bloodstream, where they are transported to the bone marrow and begin producing normal white blood cells that can produce ADA.
YESCARTA: Developed to treat a cancer called large B cell lymphoma, Yescarta was approved by the FDA in 2017 and in the E.U. in 2018. It is in clinical trials in China. Large B cell lymphoma affects white blood cells called lymphocytes. The treatment, part of an approach known as CAR-T cell therapy, uses a virus to insert a gene that codes for proteins called chimeric antigen receptors (CARs) into a patient's T cells. When these cells are reintroduced into the patient's body, the CARs allow them to attach to and kill cancer cells in the bloodstream.
ZOLGENSMA: In May 2019 the FDA approved Zolgensma for children younger than two years with spinal muscular atrophy, a neuromuscular disorder that affects about one in 10,000 people worldwide. It is one of the leading genetic causes of infant mortality. Zolgensma delivers a healthy copy of the human SMN gene to a patient's motor neurons in a single treatment.
ZYNTEGLO: Granted approval in the E.U. in May 2019, Zynteglo treats a blood disorder called beta thalassemia that reduces a patient's ability to produce hemoglobin, the protein in red blood cells that contains iron, leading to life-threatening anemia. The therapy has been approved for individuals 12 years and older who require regular blood transfusions. It employs a virus to introduce healthy copies of the gene for making hemoglobin into stem cells taken from the patient.The cells are then reintroduced into the bloodstream and transported to the bone marrow, where they begin producing healthy red blood cells that can manufacture hemoglobin.
GENE INTERFERENCE
This approach uses a synthetic strand of RNA or DNA (called an oligonucleotide) that, when introduced into a patient's cell, can attach to a specific gene or its messenger molecules, effectively inactivating them. Some treatments use an antisense method, named for one DNA strand, and others rely on small interfering RNA strands, which stop instruction molecules that go from the gene to the cell's protein factories.
DEFITELIO: This drug contains a mixture of single-strand oligonucleotides obtained from the intestinal mucosa of pigs. It was approved (with limitations) in the U.S. and the E.U. in 2017 to treat severe cases of veno-occlusive disease, a disorder in which the small veins of the liver become obstructed, in patients who have received a bone marrow transplant.
EXONDYS 51: In 2016 the FDA granted approval to Exondys 51 amid some controversy regarding its efficacy; two members of the FDA review panel resigned in protest of the decision. The therapy is designed to treat a form of Duchenne muscular dystrophy caused by mutations in the RNA that codes for the protein that helps to connect muscle fibers' cytoskeletons to a surrounding matrix. Exondys 51 is effective in treating about 13 percent of the Duchenne population.
KYNAMRO: Approved by the FDA in in 2013, Kynamro is designed to inhibit—or effectively shut down production of—a protein that helps to produce low-density lipoprotein (LDL). Injected subcutaneously, this therapy is used to lower LDL levels in patients who have dangerously high cholesterol.
MACUGEN: Age-related macular degeneration is the leading cause of vision loss in people age 60 and older. It is caused by deterioration of the center of the retina due to leaking blood vessels. Approved in the U.S., Macugen inhibits these blood vessels from growing under the retina, thus treating the disorder.
SPINRAZA: With its FDA approval in 2016, Spinraza became the first gene-based therapy for spinal muscular atrophy. The inherited disorder is caused by low levels of SMN, a key protein for the maintenance of motor neurons. Spinraza binds to RNA from a "backup" gene called SMN2, converting that RNA into instructions for making fully functioning SMN proteins.
<?>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
"As far as we know," said corresponding author Karissa Sanbonmatsu, "this is the first full 3-D structural study of any long, non-coding RNA (lncRNA) other than a partial structure." Sanbonmatsu is a structural biologist at Los Alamos National Laboratory. "A better understanding of these RNAs could lead to new strategies in regenerative medicine for people with heart conditions due to cardiovascular disease or aging."
The team used a technique called small angle X-ray scattering (SAXS) that reveals the 3-D envelope of the RNA molecule, according to Trushar Patel, a Canadian professor on the team. Next, with the help of machine learning and high-performance computing, they made atomistic models to fit inside the envelopes—this included the creation of an atomistic model that is also the longest of an isolated RNA (636 nucleotides) to date, said Doo Nam Kim, lead author on the Nature Communications paper.
"Our work represents the first step in showing that these difficult-to-image RNAs do possess 3-D structures, and that these molecular structures may very well determine how they operate," said Sanbonmatsu. "The RNA studied is called "Braveheart"—it triggers the transformation of stem cells into heart cells," she said.
Before the human genome was sequenced in 2000, it was thought that it mostly contained instructions for proteins, the workhorse molecules of human cells. Scientists were shocked to discover that less than 10 percent of the genome encoded proteins. Ever since, the other 90 percent was deemed to be "junk DNA" or "dark matter." Enter RNA, the molecular cousin of DNA. Scientists originally assumed the main purpose of RNA was simply to coordinate as a messenger for DNA in the synthesis of proteins. However, it has recently been shown that more than 90 percent of the genome encodes a new and mysterous class of RNAs, called long non-coding RNA molecules (lncRNA).
These RNA molecules help to control the turning on and off of genes; their malfunction causes birth defects, autism and even cancer in some cases. They are also key to reprogramming adult stem cells. Even though the molecules make up 90 percent of the genome, scientists have almost no idea how they work, or even what they look like. In this study, one of the largest RNA-only 3-D studies, the new 3-D images sets the stage for future studies that will shed more light on how they control genes.
<?>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d<>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
Sæsonen med brande vil starte tidligere, slutte senere, og brandene vil være mere intense. Disse effekter vil vokse over tid, men være tydelige i 2020.«
Sådan lyder en af hovedkonklusionerne i en rapport fra 2008, som blev bestilt af den australske regering, der ønskede en vurdering af effekterne af den globale opvarmning på landet.
I dag er situationen, at Australien står i flammer, præcis som forudsagt. Nogle indbyggere i Sydney går rundt med masker på, og i byen Canberra er luftkvaliteten i øjeblikket den værste noget sted på kloden – værre end notorisk forurenede Delhi.
Et område på mere end 10 millioner hektar er brændt. Til sammenligning er hele det danske landareal kun på 4,2 millioner hektar. Det danske skovareal er på 621.000 hektar.
Australien har også set 1.700 huse gå op i røg, mens 26 mennesker har mistet livet samt omkring en milliard dyr.
Advaret i 2008, 2009, 2017, 2018 og 2019
Den australske regering var fuldt ud advaret om situationen i dag. Både i rapporten fra 2008 og i efterfølgende rapporter såsom en såkaldt CSIRO-rapport fra 2009 fra landets nationale forskningscenter.
Her advarede forskerne om, at et særlig brandfarligt meteorologisk fænomen ville være op til fire gange mere sandsynligt i en fremtid med global opvarmning – og lignende advarsler blev gentaget i rapporter i 2017, 2018 og 2019, skriver Slate.com.
I dag er økonomen Ross Garnaut, der stod i spidsen for rapporten i 2008, ikke glad for, at han havde ret i sine forudsigelser. Som en kommentar til den nuværende situation siger han til SBS News:
»Jeg er mest ked af det, fordi jeg ikke kunne trænge igennem. Jeg havde fået muligheden for at fortælle australierne om emnet, og jeg var ikke god nok til at overbevise australierne om, at det var i vores nationale interesse at være medspillere i den globale kamp for at stoppe effekterne af klimaforandringer.«
CO2-kvoter og CO2-skat blev aldrig indført
Garnaut-rapporten anbefalede direkte indførelsen af CO2-kvoter, men de blev aldrig gennemført, ligesom en CO2-skat også var et forslag, der aldrig blev vedtaget af politikerne.
Den nuværende regering, og især premierminister Scott Morrison, har fået kritik for at afvise en kobling mellem global opvarmning og skovbrande, men har de seneste uger gentaget samme budskab i flere australske og internationale medier, nemlig at klimaforandringer er »en ud af mange faktorer«.
Ifølge premierministeren selv har han »altid anerkendt, at der er en forbindelse mellem disse vejrfænomener og disse mere omfattende skovbrande og effekterne af globale klimaforandringer,« lyder det blandt andre til Bloomberg.
Varmest og tørrest år nogensinde målt
I Australien startede brandene i september, en måned tidligere end normalt.
Og de har nu ødelagt et større område end brandene i Amazonas sidste år og brandene i Californien forrige år tilsammen, herunder regnskove i New South Wales og det sydlige Queensland, der historisk set aldrig brænder, fordi der er for vådt.
Den 18. december blev målt til den varmeste dag nogensinde i Australien med en maksimum-temperatur på 41,9 grader celsius. Og den 8. januar kunne landets mereteologiske institut fortælle, at 2019 både var det varmeste og tørreste år, der nogensinde var blevet målt.
To større vejrfænomener er blandt forklaringerne på brandene.
En stærk indisk Niño, også kaldet Det Indiske Ocean Dipol, skubber varmt vand væk fra Australien og mod Afrika, mens den antarktiske oscillation (SAM) har drevet varme tørre vinde fra Australiens ørkener i landets midte mod østkysten.
De to fænomener skaber tilsammen et giftigt vejrmiks, som er set før i historien, men aldrig i så lang tid.
Og i dag er de krydret med en global temperaturstigning på 1 grad celsius sammenlignet med 1910.
<?>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d<>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d<>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d<>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d<>
1d
1d
1d
1d<?>
1d
Scientists from Purdue University in the US have developed a new way of producing hydrogen from food waste.
The new method developed by scientists uses yeast to break down the food waste and turn it into clean hydrogen for further use with minimal pre-processing steps in approximately 18-24 hours.
"We wanted to create a simple way to turn all that food waste into a source of clean energy," said Robert Kramer, NiSource Charitable Foundation Professor of Energy and the Environment and Professor of Physics at Purdue University Northwest.
"Our system basically allows a user to take food waste, grind it, place it in a reactor and use our process to create hydrogen in about 18-24 hours. That's much faster than the days it takes with other methods."
Kramer has estimated that the new Purdue system could lead to a 20%-25% increase in efficiency when producing hydrogen from food waste compared with current methods.
The Professor also says the method can be easily multiplexed with solar thermal technology to make a stand-alone power source in addition to being a clean fuel source and having multiple applications in the agro-food and transportation industries.
Until now, production of hydrogen for use as clean fuel has been mainly through bacterial degradation of food waste, which can lead to slow production rates and complex pre-processing of the raw material.
The Purdue University team worked with the Purdue Research Foundation Office of Technology Commercialisation to patent the technology.<?>
Watergen's GENNY runs on a simple mechanism. It draws moist air in through a filter at the back of the device like a dehumidifier then cleans and dispenses it out the front like a standard water cooler. (As a bonus, it'll purify the air around it too). It can dispense 13 liters of water per day with 9 KWH of energy and works in 15-40 degrees celsius with a relative humidity of more than 25 per cent.
The latest model, Solar GENNY, runs on the same technology but runs fully on natural energy, which is a major step forward. It can assist with living off the grid but could have real value delivering precious drinking water to less-developed areas or crisis zones.
Packaged with the four 23-foot solar panels to run it — provided by a third party solar company — and including installation costs, it should cost $5-8,000. While it's neither compact nor cheap at this moment, the prospect of a no-waste solution to the world's water scarcity warrants attention. It essentially turns air and sun into clean water.
<?>
1d
Cast your mind back a decade or so and consider how the future looked then. A public horizon of Obama-imbued "yes we can" and a high tide of hope and tolerance expressed in the London Olympics provides one narrative theme; underlying austerity-induced pressure another. Neither speaks directly to our current world of divisive partisan politics, toxic social media use, competing facts and readily believed fictions.
This should be instructive. The future is made, not discovered, and yet we are constantly confounded by the future as it becomes the present. What we believe, say, do, organise and vote for matter, but the world they matter to constantly eludes our grasp. We often stumble into futures we would rather avoid. Our ecological and climatological future represents one such horizon and whether and how we will work, another.
Organisations are also constantly trying to own the future by mapping out what it will mean for us. The "fourth industrial revolution" is the latest version of this. It is commonly defined as a combination of new technologies, including artificial intelligence (AI), machine learning, natural language coding, robotics, sensors, cloud computing, nano-technology, 3D printing and the internet of things. According to proponents of the fourth industrial revolution, these technologies are set to transform the societies we live and the economies we work in. And apparently, this is likely to be well underway by 2030.
It's important to grasp, though, that the fourth industrial revolution is just a concept, an attempt to capture the meaning and significance of what seems to be occurring. The idea incites anxiety-inducing headlines regarding threats to employment and a general theme of positivity regarding the benefits of technology.
A shiny future
The main proponents of the idea of a fourth industrial revolution are think tanks and consultancies working with modellers, economists and tech-experts (and of course technology companies themselves). This work provides the themes, insights and much of the analysis of data that informs current government policy in the form of industrial strategy.
At the heart of this is the World Economic Forum's work, spearheaded by its Executive Chairman Klaus Schwab, and that of the McKinsey Global Institute. The focus of both is weighted towards expressing the benefits of imminent transformations if we invest quickly and invest heavily.
For example, imagine a world where your toilet bowl tells your fridge that your cholesterol is high. Your fridge, in turn, both adjusts your order for dairy products that week (delivered by automated vehicle or drone from a grocery warehouse) and sends an alert to the healthcare AI whose database monitors your cardiovascular system. This AI, in turn, liaises with your home hub chatbot facility (which rebukes you and suggests you cut down on fats and make more use of your home gym subscription) and, if deemed necessary, sets up a home visit or virtual reality appointment with your local nurse or doctor.
According to the fourth industrial revolution literature, this, like many other possibilities, is science fiction on the cusp of being science fact. It is a commercialised future, a cradle to grave system. A system that, apparently, may help us survive our profligate past and present since the fourth industrial revolution also promises a sustainable future, where a connected set of technologies creates the possibility of controlled energy and resource use, minimal waste creation and maximal recycling.
But these think tanks and consultancies are hardly going to be held directly responsible for the future they help to produce. They are not sinister organisations, but nor are they neutral. The "fourth industrial revolution" is not simply an opportunity. It matters what kind of opportunity it is for whom, and under what terms. And this is discussed much more rarely.
A future for whom?
The emphasis on benefits and the focus on the need for investment subtly distracts from the core issue of who will own the basic infrastructure of our futures. Large corporations aim to control intellectual property for technologies that will influence every aspect of life.
At the same time, those writing about the fourth industrial revolution recognise that there might be what they call "technological unemployment". Current claims regarding the likely rate of job displacement are mixed. Some research claim between 30% and 50% of current forms of employment could disappear. Some suggests around 10% is more likely.
But the implicit message conveyed by corporations and consultancies, despite the fact that this will affect most sectors of society, is that "the future is coming and you'd better get used to it". And government messaging and policy has tended to absorb this point of view. For government, the opportunities have been translated into a language of competitive threats: "If we do not do these things, others will." This subtly focuses attention on inevitable economic consequences without providing scope to consider the broader social ramifications that might need to be managed.
In the UK, for example, there is, as yet, no broad government initiative for public education, consultation and deliberation regarding a subject that may involve profound changes to our societies. Only the House of Lords Select Committee on Artificial Intelligence has flagged this. The focus otherwise has been on "employability". And the main emphasis has tended to be on individual responsibility. This assumes there will be jobs we can do if we retrain, enhance our human capital, compete with robot capital, and get used to collaborating with technologies.
And yet fourth industrial revolution technologies could put the basic functional relations of a capitalist economy at risk. Waged labour is what allows consumption, which in turn becomes profit for companies, which in turn maintains companies, wage labour, and the capacity to contribute taxes. If adoption of new technologies is rapid and pervasive, then the displacement of human workers may overwhelm the capacity of economies to provide alternative forms of work.
This is one extreme possibility, but it is one that current government policy is doing little to confront. At the moment, in the UK, only trade unions and some fringes of the Labour Party are thinking about the scope inherent in new technology for different kinds of societies that might liberate us from work. This must change.
<?>
- Police in San Diego have used facial recognition for seven years, collecting over 65,000 face scans in the past three years alone — but the program hasn't been connected to a single arrest.
- The program has now been shuttered thanks to a new California law banning the use of facial recognition by mobile devices used by police.
- However, police departments across the country are still embracing facial recognition as a tool to track people and identify suspects.
Police in San Diego have been using facial recognition for seven years, and over 65,000 face scans have been collected by law enforcement in San Diego county in the past three years alone. But San Diego Police Department's use of facial-recognition technology has not been connected to a single arrest, a police spokesperson told Fast Company.
When reached for comment by Business Insider, a San Diego Police Department spokesperson said that SDPD officers were not able to identify any cases in which facial recognition led to an arrest, but added that it's possible such an arrest was made in the past that the department wasn't able to immediately identify.
San Diego is one of many major cities across the US to embrace facial recognition. While the tool has been heavily hyped for its potential to track people and identify possible suspects, Fast Company's findings call the effectiveness of facial recognition into question.
Critics of the technology have also pointed to studies suggesting that it's biased against women and people of color. A federal study published last month found that facial recognition algorithms were up to 100 times more likely to misidentify black people and Asian people than white men, and women were more likely to be misidentified across the board.
San Diego's facial recognition program was shuttered on January 1 in accordance with a new California law that bans government agencies from using facial recognition on mobile devices used by police for the next three years. The SDPD spokesperson told Business Insider that face scans it captured have not been stored for future use.
The city was one of the first major municipalities in the US to embrace facial recognition in 2013. At the time, Reveal News, a nonprofit investigative outlet, reported that San Diego law enforcement heralded it as a boon to preventing crime.
That prediction doesn't appear to have come to fruition. When California's facial recognition ban went into effect this month, a police spokesperson told Fast Company that it was unlikely to have "much of an impact on our department."
<?>
A coyote attacked a 5-year-old boy near the Peggy Notebaert Nature Museum in Chicago on Wednesday, sending him to the hospital.
He was in stable condition, the Chicago Fire Department reported.
Later that day, a coyote bit an adult man on the buttocks, according to news accounts. The man showed up at another Chicago hospital with a minor injury. Since a coyote had not been caught, it was not clear whether the same animal had assaulted both people.
The individual attacks, particularly of a child, are frightening. Although such events are rare, they are now common enough in major urban areas to be familiar. The reason is the extraordinary number of coyotes now living in the midst of densely settled cities.
Coyotes have long been present in much of North America, but since 1900 their range has grown enormously, expanding east, north and south. In more recent decades, they have moved into urban areas. Coyotes have been colonizing the canyons of Los Angeles at least since the 1970s. First seen in the Bronx in the 1990s, coyotes have grown in numbers on the streets of Manhattan, and have attacked children in the New York suburbs.
<?>
1d
1d
A sophisticated new screening platform developed by scientists at Scripps Research has enabled them to discover a set of drug-like compounds, including an ingredient found in sore throat lozenges, that may powerfully protect brain cells from dangerous stresses found in Alzheimer's and other neurodegenerative diseases.
The screening platform, described in a paper in Science Advances, allows researchers for the first time to rapidly test "libraries" of thousands of molecules to find those that provide broad protection to mitochondria in neurons. Mitochondria are tiny oxygen reactors that supply cells with most of their energy. They are especially important for the health and survival of neurons. Mitochondrial damage is increasingly recognized as a major factor, and in some cases a cause, for diseases of neuronal degeneration such as Alzheimer's, Parkinson's, and ALS.
The scientists, in an initial demonstration of their platform, used it to rapidly screen a library of 2,400 compounds, from which they found more than a dozen that boost the health of neuronal mitochondria and provide broad protection from stresses found in neurodegenerative disorders.
The researchers are now testing the most potent of these mitochondria-protectors in animal models of Alzheimer's, amyotrophic lateral sclerosis, and other diseases, with the ultimate goal of developing one or more into new drugs.
"It hasn't yet been emphasized in the search for effective therapeutics, but mitochondrial failure is a feature of many neurodegenerative disorders and something that must be corrected if neurons are to survive," says principal investigator Ronald Davis, PhD, professor in the Department of Neuroscience at Scripps Research. "So I'm a big believer that finding mitochondria-protecting molecules is the way to go against these diseases."
Scientists in prior studies have developed screens for molecules that can enhance mitochondrial function, but only by focusing on mitochondria in cells from outside the brain. A screening system that measures mitochondrial health in mature neurons requires cultures of such neurons, which are relatively difficult to maintain — in part because they do not divide to make new neurons. Davis was convinced, however, that only this more difficult approach, which others including pharmaceutical researchers have avoided, would enable the discovery of compounds that protect brain cells by protecting their mitochondria.
The screening system developed by Davis and his team uses cultured neurons from mouse brains in which mitochondria are labeled with fluorescent tags. Sophisticated microscope imaging and semi-automated image analysis enables the researchers to quickly record mitochondrial numbers, shapes and other visible markers of health in the neurons before and after exposure to different compounds.
In an initial test, the team found that compounds with reported benefits for mitochondria in other cell types had no obvious positive effects for mitochondria in neurons. The researchers then screened their library of 2,400 compounds, which included many existing drug compounds, and found 149 with significant positive effects on neuronal mitochondria.
With further tests the scientists winnowed these "hits" down to a much smaller number, and found several that could robustly protect mouse neuron mitochondria from three stresses known to harm mitochondria in Alzheimer's: small, toxic clusters of the amyloid beta protein; the neurotransmitter glutamate, which can excite neurons to death; and peroxide, a highly reactive molecule that can be released from damaged mitochondria and go on to harm healthy mitochondria.
The compounds with beneficial effects protected the neuronal mitochondria in some ways more than others, and evidently worked via a variety of biological mechanisms. For example, dyclonine, an anesthetic found in some sore-throat products, protected cultured neurons against glutamate and peroxide toxicity. Dyclonine also increased the energy production of healthy mitochondria as well as the activity of their host neurons' synapses — connection points to other neurons. Dyclonine seemed so promising that the researchers put it in the water supply of live mice, and again found evidence that it powerfully boosted the health of the mitochondria in the animals' brains.
"It remains a mystery why dyclonine and other local anesthetics have such effects on mitochondria in neurons — we certainly didn't anticipate this," Davis says. "But the compounds we identified give us strong hope that we'll see beneficial effects when we test them in animal models of specific neurodegenerative diseases, as we're now doing."
Story Source:
Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.
Journal Reference:
- Boglarka H. Varkuti, Miklos Kepiro, Ze Liu, Kyle Vick, Yosef Avchalumov, Rodrigo Pacifico, Courtney M. MacMullen, Theodore M. Kamenecka, Sathyanarayanan V. Puthanveettil, Ronald L. Davis. Neuron-based high-content assay and screen for CNS active mitotherapeutics. Science Advances, 2020; 6 (2): eaaw8702 DOI: 10.1126/sciadv.aaw8702
<?>
1d
1d<>
"Habitual tea consumption is associated with lower risks of cardiovascular disease and all-cause death," said first author Dr. Xinyan Wang, Chinese Academy of Medical Sciences, Beijing, China. "The favourable health effects are the most robust for green tea and for long-term habitual tea drinkers."
The analysis included 100,902 participants of the China-PAR project2 with no history of heart attack, stroke, or cancer. Participants were classified into two groups: habitual tea drinkers (three or more times a week) and never or non-habitual tea drinkers (less than three times a week) and followed-up for a median of 7.3 years.
Habitual tea consumption was associated with more healthy years of life and longer life expectancy.
For example, the analyses estimated that 50-year-old habitual tea drinkers would develop coronary heart disease and stroke 1.41 years later and live 1.26 years longer than those who never or seldom drank tea.
Compared with never or non-habitual tea drinkers, habitual tea consumers had a 20% lower risk of incident heart disease and stroke, 22% lower risk of fatal heart disease and stroke, and 15% decreased risk of all-cause death.
The potential influence of changes in tea drinking behaviour were analysed in a subset of 14,081 participants with assessments at two time points. The average duration between the two surveys was 8.2 years, and the median follow-up after the second survey was 5.3 years.
Habitual tea drinkers who maintained their habit in both surveys had a 39% lower risk of incident heart disease and stroke, 56% lower risk of fatal heart disease and stroke, and 29% decreased risk of all-cause death compared to consistent never or non-habitual tea drinkers.
Senior author Dr. Dongfeng Gu, Chinese Academy of Medical Sciences, said: "The protective effects of tea were most pronounced among the consistent habitual tea drinking group. Mechanism studies have suggested that the main bioactive compounds in tea, namely polyphenols, are not stored in the body long-term. Thus, frequent tea intake over an extended period may be necessary for the cardioprotective effect."
In a subanalysis by type of tea, drinking green tea was linked with approximately 25% lower risks for incident heart disease and stroke, fatal heart disease and stroke, and all-cause death. However, no significant associations were observed for black tea.
Dr. Gu noted that a preference for green tea is unique to East Asia. "In our study population, 49% of habitual tea drinkers consumed green tea most frequently, while only 8% preferred black tea. The small proportion of habitual black tea drinkers might make it more difficult to observe robust associations, but our findings hint at a differential effect between tea types."
Two factors may be at play. First, green tea is a rich source of polyphenols which protect against cardiovascular disease and its risk factors including high blood pressure and dyslipidaemia. Black tea is fully fermented and during this process polyphenols are oxidised into pigments and may lose their antioxidant effects. Second, black tea is often served with milk, which previous research has shown may counteract the favourable health effects of tea on vascular function.
Gender-specific analyses showed that the protective effects of habitual tea consumption were pronounced and robust across different outcomes for men, but only modest for women. Dr. Wang said: "One reason might be that 48% of men were habitual tea consumers compared to just 20% of women. Secondly, women had much lower incidence of, and mortality from, heart disease and stroke. These differences made it more likely to find statistically significant results among men."
She added: "The China-PAR project is ongoing, and with more person-years of follow-up among women the associations may become more pronounced."
The authors concluded that randomised trials are warranted to confirm the findings and provide evidence for dietary guidelines and lifestyle recommendations.
Story Source:
Materials provided by European Society of Cardiology. Note: Content may be edited for style and length.
Journal Reference:
- Xinyan Wang, Fangchao Liu, Jianxin Li, Xueli Yang, Jichun Chen, Jie Cao, Xigui Wu, Xiangfeng Lu, Jianfeng Huang, Ying Li, Liancheng Zhao, Chong Shen, Dongsheng Hu, Ling Yu, Xiaoqing Liu, Xianping Wu, Shouling Wu, Dongfeng Gu. Tea consumption and the risk of atherosclerotic cardiovascular disease and all-cause mortality: The China-PAR project. European Journal of Preventive Cardiology, 2020; 204748731989468 DOI: 10.1177/2047487319894685
<?>
A drug designed to tackle diabetes could also be repurposed as the first treatment to prevent miscarriage by targeting the lining of the womb itself, according to a clinical trial led by the University of Warwick.
The treatment works by increasing the amount of stem cells in the lining of the womb, improving conditions in the womb to support pregnancy.
The research by Warwick Medical School is reported today (9 January) in the journal EBioMedicine from research conducted with University Hospitals Coventry and Warwickshire and supported by the NIHR Coventry and Warwickshire Clinical Research Facility. The research was funded by and took place at Tommy's National Miscarriage Research Centre.
Recurrent miscarriage is defined as the loss of two or more consecutive pregnancies, with additional miscarriages decreasing the likelihood of a successful pregnancy. Previous research by the Warwick team revealed that a lack of stem cells in the womb lining is causing thousands of women to suffer from recurrent miscarriages. The team also demonstrated that stem cells protect specialised cells, called decidual cells, from excessive stress and inflammation. Decidual cells surround the implanting embryo and excessive stress can cause breakdown of the womb lining in pregnancy.
A new class of diabetes drugs called gliptins targets an enzyme involved in the recruitment of circulating stem cells to the womb. The researchers investigated whether inhibiting this enzyme, called DPP4, using a particular drug, sitagliptin, would improve conditions in the womb for pregnancy.
In a pilot clinical trial, thirty-eight women aged 18 to 42 who had experienced a large number of recurrent miscarriages (average five) were given either an oral course of sitagliptin or a placebo for three menstrual cycles. Biopsies of the womb were taken at the start of the course of treatment and afterwards to determine the number of stem cells present before and after the course.
They found an average increase in stem cell count of 68% in those women who took the full course of sitagliptin. This compares to no significant increase in those in the control group receiving an identical placebo pill. They also saw a 50% decrease in the number of 'stressed' cells present in the lining of the womb. There were minimal side effects for the participants.
The researchers now hope to take the treatment to clinical trial and, if successful, it would be the first targeted specifically at the lining of the womb to prevent miscarriage.
Professor Jan Brosens, of Warwick Medical School and Consultant in Reproductive Health at University Hospitals Coventry and Warwickshire NHS Trust, said: "There are currently very few effective treatments for miscarriage and this is the first that aims at normalising the womb before pregnancy. Although miscarriages can be caused by genetic errors in the embryo, an abnormal womb lining causes the loss of chromosomal normal pregnancies. We hope that this new treatment will prevent such losses and reduce both the physical and psychological burden of recurrent miscarriage."
Professor Siobhan Quenby from Warwick Clinical Trials Unit and an Honorary Consultant at University Hospital Coventry and Warwickshire NHS Trust, said: "We have improved the environment that an embryo develops in and in doing so we hope to improve the chances of a successful pregnancy. Although this research was specifically designed to test whether we could increase the presence of stem cells in the womb, follow-up of participants found that there were no further losses of normal pregnancies in those who took sitagliptin. These are very early results and the treatment now needs to be further tested in a large-scale clinical trial."
Jane Brewin, Chief Executive at Tommy's said: "For far too long it has often been said by many health professionals that miscarriage is not preventable, and parents have been left with little hope given the paucity of treatment options available. This situation prompted Tommy's to invest in the Tommy's National Centre for Miscarriage Research and this breakthrough research by the world leading team at Warwick shows great promise for an effective treatment which will reduce miscarriage and possibly later pregnancy loss too. A large-scale trial is needed to verify the findings and we hope that this will get underway quickly."
Stem cells play a key role in creating the decidual cells in the womb lining which support the placenta throughout pregnancy. Insufficient stem cells in the womb lining leads to an excess of stressed and inflammatory decidual cells, which in turn may cause placental bleeding and miscarriage. Sitagliptin was effective not only in increasing stem cells in the womb lining but also decreasing the abundance of stressed decidual cells.
Story Source:
Materials provided by University of Warwick. Note: Content may be edited for style and length.
Journal Reference:
- Shreeya Tewary, Emma S. Lucas, Risa Fujihara, Peter K. Kimani, Angela Polanco, Paul J. Brighton, Joanne Muter, Katherine J. Fishwick, Maria José Minhoto Diniz Da Costa, Lauren J. Ewington, Lauren Lacey, Satoru Takeda, Jan J. Brosens, Siobhan Quenby. Impact of sitagliptin on endometrial mesenchymal stem-like progenitor cells: A randomised, double-blind placebo-controlled feasibility trial. EBioMedicine, 2020; 102597 DOI: 10.1016/j.ebiom.2019.102597
Cite This Page:
<?>
1d
1d<>
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d<>
1d
1d
1d
1d
We all will experience it at some point, unfortunately: The older we get the more our brains will find it difficult to learn and remember new things. What the reasons underlying these impairments are is yet unclear but scientists at the Center for Regenerative Therapies of TU Dresden (CRTD) wanted to investigate if increasing the number of stem cells in the brain would help in recovering cognitive functions, such as learning and memory, that are lost during ageing.
To investigate this, the research group led by Prof. Federico Calegari used a method developed in his lab to stimulate the small pool of neural stem cells that reside in the brain in order to increase their number and, as a result, to also increase the number of neurons generated by those stem cells. Surprisingly, additional neurons could survive and form new contacts with neighbouring cells in the brain of old mice. Next, the scientists examined a key cognitive ability that is lost, similarly in mice and in humans, during ageing: navigation.
It is well known that individuals learn to navigate in a new environment in a different way depending on whether they are young or old. When young, the brain can build and remember a cognitive map of the environment but this ability fades away in older brains. As an alternative solution to the problem, older brains without a cognitive map of the environment need to learn the fixed series of turns and twists that are needed to reach a certain destination. While the two strategies may superficially appear similar, only a cognitive map can allow individuals to navigate efficiently when starting from a new location or when in need of reaching a new destination.
Would boosting the number of neurons be sufficient to counteract the decreasing performance of the brain in navigation and slow down this ageing process? The teams of Prof. Calegari (CRTD) together with Prof. Gerd Kempermann (German Center for Neurodegenerative Diseases DZNE / CRTD) and Dr. Kentaroh Takagaki (Otto von Guericke University Magdeburg) found the answer to this challenging question and published it this week in the scientific journal Nature Communications.
The answer is "Yes": Old mice with more stem cells and neurons recovered their lost ability to build a map of the environment and remembered it for longer times making them more similar to young mice. Even better, when neural stem cells were stimulated in the brain of young mice, cognitive impairments were delayed and memory was better preserved over the entire course of the animal natural life.
In young individuals, a brain area called the hippocampus is crucial for remembering places and events, and is also responsible for creating maps of new environments. However, old individuals use other structures that are more related to the development of habits. It was very interesting to see that adding more neurons in the hippocampus of old mice allowed them to use strategies typical of young animals. It was not only about how fast they were learning but, rather, how different the learning process itself was ," explains Gabriel Berdugo-Vega, first author of the study.
"Also humans have a few stem cells in the brain and these stem cells are known to severely reduce in numbers over the course of life. Identifying the causes underlying cognitive deficits in ageing and rescuing them is crucial for our rapidly ageing societies. Our work demonstrates that age-related impairments can be rescued by hijacking the endogenous neurogenic potential of the brain, thus, rejuvenating its function. Being a human myself with my own stem cells and being the senior author of this study, I felt that I had a personal interest in this topic." says Prof. Federico Calegari, senior author of this study.
The research group of Prof. Federico Calegari focuses on mammalian neural stem cells in the context of development, evolution and cognitive function at the CRTD. The institute is the academic home for scientists from more than 30 nations. Their mission is to discover the principles of cell and tissue regeneration and leveraging this for recognition, treatment and reversal of diseases. The CRTD links the bench to the clinic, scientists to clinicians to pool expertise in stem cells, developmental biology, gene-editing and regeneration towards innovative therapies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease, haematological diseases such as leukaemia, metabolic diseases such as diabetes, retina and bone diseases.
This study was funded by TU Dresden / CRTD through the German Excellence Initiative, the German Research Foundation and a European grant from the H2020 programme. In addition, it was supported by the Faculty of Natural Sciences of Otto-von-Guericke University Magdeburg, the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB) and the German Center for Neurodegenerative Diseases (DZNE).
Story Source:
Materials provided by Technische Universität Dresden. Note: Content may be edited for style and length.
Journal Reference:
- Gabriel Berdugo-Vega, Gonzalo Arias-Gil, Adrian López-Fernández, Benedetta Artegiani, Joanna M. Wasielewska, Chi-Chieh Lee, Michael T. Lippert, Gerd Kempermann, Kentaroh Takagaki, Federico Calegari. Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-019-14026-z
<?>
1d
1d
1d
1d
1d
Vil du være med til at finde de mest interessante nyheder? Send email herom til BioNyt
Se nyheder fra en tidligere dato
Tegn abonnement på
BioNyt Videnskabens Verden (www.bionyt.dk) er Danmarks ældste populærvidenskabelige tidsskrift for naturvidenskab. Det er det eneste blad af sin art i Danmark, som er helliget international forskning inden for livsvidenskaberne.
Bladet bringer aktuelle, spændende forskningsnyheder inden for biologi, medicin og andre naturvidenskabelige områder som f.eks. klimaændringer, nanoteknologi, partikelfysik, astronomi, seksualitet, biologiske våben, ecstasy, evolutionsbiologi, kloning, fedme, søvnforskning, muligheden for liv på mars, influenzaepidemier, livets opståen osv.
Artiklerne roses for at gøre vanskeligt stof forståeligt, uden at den videnskabelige holdbarhed tabes.
Recent Comments