Losing Weight With Supplements: Fish Oil May Produce Microbes That ‘Protect’ Against Weight Gain And Inflammation


Fish Oil
Fish oil benefits spread from the brain, heart, and down to the stomach.

Fish oil has been shown to benefit the human body, from improved cognitive abilities to the heart’s pumping efficiency — but it may be fish oil’s ability to alter an individual’s gut bacteria that makes it an ideal weight loss treatment. Researchers from the University of Gothenburg in Sweden compared fish oil’s effect on the gut to lard, another type of dietary fat. Their findings, published in the journal Cell Metabolism, reveal the impact, for better or worse, fish oil and lard respectively have on gut bacteria.

“We wanted to determine whether gut microbes directly contribute to the metabolic differences associated with diets rich in healthy and unhealthy fats,” the study’s co-author Dr. Robert Caesar, a researcher at the University of Gothenburg, said in a press release. “Our goal is to identify interventions for optimizing metabolic health in humans.” So Caesar and his colleagues fed mice either a diet of lard or fish oil for 11 weeks, while monitoring signs of metabolism changes.

They found lard promoted the growth of bacteria Bilophila, which is linked to gut inflammation. Fish oil, on the other hand, increased the amount of bacteria Akkermansia muciniphila, which reduces weight gain and improves blood sugar metabolism.

Next, researchers transplanted fecal matter (known as a “fecal transplant”) from mice on a lard diet into mice on a fish diet and vice-versa. After they transferred all of the fecal matter containing the mice’s diet-affected gut microbes, researchers were able to see the power of microbes in action. Apparently, mice that were on a lard diet but received a fish oil fecal transplant into their gut were better protected against weight gain and inflammation. But mice that were on a fish oil diet and received lard-containing fecal matter experienced inflammation and obesity. The fecal transplants confirmed that gut microbiome can cause certain health problems and help individuals recover from them depending upon the type of diet feeding the gut.

Both fish oil and lard are considered fat, but they’re not created equal. Lard is a fat that comes from pigs, commonly used in baking and as a spread for breads. According to the American Heart Association, it contains 40 percent saturated fat, which can be  harmful to the heart as it increases blood pressure, “bad” LDL cholesterol, and fatty build-up in the arteries.

Fish oil is quite the opposite. Researchers at Harvard Medical School found that fish oil supplements are an easy way to protect the heart, ease inflammation, and even improve mental health and lengthen a person’s lifespan. Omega-3 fatty acid deficiencies, fish oil’s main ingredient, have been linked to heart disease, certain cancers, mental health disorders, and arthritis. Despite all of fish oil’s benefits, researchers still didn’t expect it to change the gut microbiome community into a powerful weight loss and anti-inflammatory treatment.

“We were surprised that the lard and the fish oil diet, despite having the same energy content and the same amount of dietary fiber — which is the primary energy source for the gut bacteria — resulted in fundamentally different gut microbiota communities,” Caesar said. “The microbiota per se had such large effects on health.”

Discovering that the bacteria A. muciniphila can be enhanced in the body has led the research team to study its potential in weight management. Their next step will be determining if the bacteria can be turned into a supplement and combined with a specific diet to “optimize health outcomes.”

Source: Backhed F, Caesar R, Tremaroli V, Kovatcheva-Datchary P, and Cani PD. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metabolism. 2015

GOOGLE PROJECT SUNROOF


Google Project Sunroof calculates rooftop solar potential, by using Google Maps, is mapping the planet’s solar potential, one rooftop at a time.

It figures out “how much sun falls on a roof and takes into account stuff like the angle of the roof, the weather, and obstructions like trees and chimneys. Then it uses those measurements to figure out how many panels you’d probably need and how much you could save on your electric bill, including solar incentives in your area. You can see how buying or leasing panels affects your savings, and then send your estimate to installers in your area, instantly.”

Project Sunroof, for the moment, works in Boston, the San Francisco Bay Area, and Fresno. But anyone can sign up to find out when it expands to their neighborhood.

Watch the video. URL: https://youtu.be/_BXf_h8tEes

WHY CANNABIS IS THE FUTURE OF MEDICINE


The future of medicine rests on the the fundamental right we all have to use things that spring from the Earth naturally as healing agents. Why should cannabis, used for at least 10000 years by humankind to alleviate suffering, be excluded from this inexorable mandate?

The politics of cannabis are exceedingly complex, and yet the truth is simple: this freely growing plant heals the human body – not to mention provides food, fuel, clothing and shelter, if only we will let it perform its birthright. In a previous article, we investigated the strange fact that the human body is in many ways pre-designed, or as it were, pre-loaded with a receptiveness to cannabis’ active compounds — cannabinoids — thanks to its well documented endocannabinoid system.

But the medical-industrial complex in the U.S. does not want you to use these freely growing compounds. They threaten its very business model and existence. Which is why it synergizes so naturally with the burgeoning privatized prison sector, which now has the dubious title of having the highest incarceration rate in the world. The statistics don’t lie:

“far surpassing any other nation. For every 100,000 Americans, 743 citizens sit behind bars. Presently, the prison population in America consists of more than six million people, a number exceeding the amount of prisoners held in the gulags of the former Soviet Union at any point in its history.”

According to a recent Al-Jeezera editorial, “One explanation for the boom in the prison population is the mandatory sentencing imposed for drug offences and the “tough on crime” attitude that has prevailed since the 1980s.”

Cannabis/marijuana is presently on the DEA’s Schedule 1 list.  Since 1972, cannabis has been listed on the Schedule I of the Controlled Substances Act, the most tightly restricted category reserved for drugs which have “no currently accepted medical use”. Opioids, stimulants, psychedelics and a few antidepressants now populate this list of substances that can put you in jail for possessing without a prescription.

The notion that marijuana has no ‘medicinal benefits’ is preposterous, actually. Since time immemorial it has been used as a panacea (‘cure-all’). In fact, as far back as 2727 B.C., cannabis was recorded in the Chinese pharmacopoeia as an effective medicine, and evidence for its use as a food, textile and presumably as a healing agent stretch back even further, to 12,000 BC.[1]

When it comes to cannabis’ medical applications, cannabis’ ‘healing properties’ is a loaded term. In fact, it is extremely dangerous, as far as the medical industrial complex goes, who has the FDA/FTC to enforce it’s mandate: anything that prevents, diagnoses, treats or cures a disease must be an FDA approved drug by law, i.e. pharmaceutical agents which often have 75 or more adverse effects for each marketed and approved “therapeutic” effect.

Indeed, the dominant, drug-based medical system does not even acknowledge the body’s healing abilities, opting for a view that looks at most bodily suffering as fatalistic, primarily genetically based, and resulting from dysfunction in the mechanical design of a highly entropic ‘bag of enzymes and proteins’ destined to suffer along the trajectory of time.

And so, an at least two trillion dollar a year industry stands between you and access to the disease alleviating properties of this humble plant.

As Emerson said, “a weed is an herb whose virtues have yet to be discovered,” and yet, by this definition, cannabis is not a weed, but given that is has been extensively researched and used for thousands of years for a wide range of health conditions, it should be considered and respected as a medicinal herb and food. Sadly, the fact that the whole herb is non-patentable is the main reason why it is still struggling to gain approval from the powers that be.

Let’s look at the actual, vetted, published and peer-reviewed research – bullet proof, if we are to subscribe to the ‘evidence-based’ model of medicine – which includes over 100 proven therapeutic actions of this amazing plant, featuring the following:

    • Multiple Sclerosis
    • Tourette Syndrome
    • Pain
    • Obsessive Compulsive Disorder
    • Brachial Plexus Neuropathies
    • Insomnia
    • Multiple Splasticity
    • Memory Disorders
    • Social Anxiety Disorders
    • Amyotrophic Lateral Sclerosis
  • Inflammatory Bowel Disease
  • Cancer
  • Opiate Addiction
  • Anorexia
  • Bladder Dysfunction
  • Bronchial Asthma
  • Chemotherapy-induced Harm
  • Constipation
  • Crack Addiction
  • Dementia
  • Fibromyalgia
  • Glaucoma
  • Heroin Addiction
  • Lymphoma
  • Nausea
  • Neuropathy
  • Obesity
  • Phantom Limb
  • Spinal Cord Injuries
  • Endotoxemia
  • Myocardia Infarction (Heart Attack)
  • Oxidative Stress
  • Diabetes: Cataract
  • Tremor
  • Cardiac Arrhythmias
  • Fatigue
  • Fulminant Liver Failure
  • Low Immune Function
  • Aging
  • Alcohol Toxicity
  • Allodynia
  • Arthritis: Rheumatoid
  • Ascites
  • Atherosclerosis
  • Diabetes Type 1
  • High Cholesterol
  • Liver Damage
  • Menopausal Syndrome
  • Morphine Dependence
  • Appetite Disorders
  • Auditory Disease
  • Dystonia
  • Epstein-Barr infections
  • Gynecomasia
  • Hepatitis
  • Intestinal permeability
  • Leukemia
  • Liver Fibrosis
  • Migraine Disorders
  • Oncoviruses
  • Psoriasis
  • Thymoma

Moreover, this plant’s therapeutic properties have been subdivided into the following 40+ pharmacological actions:

  • Analgesic (Pain Killing)
  • Neuroprotective
  • Antispasmodic
  • Anxiolytic
  • Tumor necrosis factor inhibitor
  • Anti-inflammatory
  • Antiproliferative
  • Apoptotic
  • Chempreventive
  • Antidepressive
  • Antiemetic
  • Bronchodilator
  • Anti-metastatic
  • Anti-neoplastic
  • Antioxidant
  • Cardioprotective
  • Hepatoprotective
  • Anti-tumor
  • Enzyme inhibitor
  • Immunomodulatory
  • Anti-angiogenic
  • Autophagy up-regulation
  • Acetylocholinesterase inhibitor
  • Anti-platelet
  • Calcium channel blocker
  • Cell cycle arrest
  • Cylooxygenase inhibitor
  • Glycine agents
  • Immunomodulatory: T-Cell down-regulation
  • Intracellular adhesion molecule-1 inducer
  • Matrix mettaproteinase-1 inhibitor
  • Neuritohgenic
  • Platelet Aggregration Inhibito
  • Vascular Endothelial Growth Factor A inhibitor
  • Anti-apoptotic
  • Anti-proliferative
  • Anti-psychotic
  • Antiviral
  • Caspase-3 activation
  • Chemosensitizer
  • Immunosupressive agent
  • Interleukin-6 upregulation
  • Tumor suppressor protein p53 upregulation

Thanks to modern scientific investigation, it is no longer considered strictly ‘theoretical’ that cannabis has a role to play in medicine. There is a growing movement to wrench back control from the powers that be, whose primary objectives appear to be the subjection of the human body in order to control the population (political motives) — what 20th century French philosopher Michel Foucault termed biopower, and not to awaken true healing powers intrinsic within the body of all self-possessed members of society. Even the instinct towards recreational use – think of the etymology: to re-create – should be allowed, as long as those who choose to use cannabis instead of tobacco and alcohol (and prescription drugs) do not cause harm to themselves or others. How many deaths are attributed to cannnabis each year versus these other societally approved recreational agents, not to mention prescription drugs, which are the 3rd leading cause of death in the developed world?

Ultimately, the politics surrounding cannabis access and the truth about its medicinal properties are so heavily a politicized issue that it is doubtful the science itself will prevail against the distorted lens of media characterizations of it as a ‘dangerous drug,’ and certainly not the iron-clad impasse represented by federal laws against its possession and use. All we can do is to advocate for the fundamental rights we all possess as free men and women, and our inborn right towards self-possession, i.e as long as what we do does not interfere with the choices and rights of others, we should be free to use an herb/food/textile that sprouts freely and grows freely from this earth, as God/Nature as freely made available.

I think people need to be educated to the fact that marijuana is not a drug. Marijuana is an herb and a flower. God put it here. If He put it here and He wants it to grow, what gives the government the right to say that God is wrong?

~ Willie Nelson

“Why is marijuana against the law? It grows naturally upon our planet. Doesn’t the idea of making nature against the law seem to you a bit . . . unnatural?” – Bill Hicks

SOAKING UP CARBON DIOXIDE AND TURNING IT INTO VALUABLE PRODUCTS


A molecular system that holds great promise for the capture and storage of carbon dioxide has been modified so that it now also holds great promise as a catalyst for converting captured carbon dioxide into valuable chemical products. Researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) have incorporated molecules of carbon dioxide reduction catalysts into the sponge-like crystals of covalent organic frameworks (COFs). This creates a molecular system that not only absorbs carbon dioxide, but also selectively reduces it to carbon monoxide, which serves as a primary building block for a wide range of chemical products including fuels, pharmaceuticals and plastics.

“There have been many attempts to develop homogeneous or heterogeneous catalysts for carbon dioxide, but the beauty of using COFs is that we can mix-and-match the best of both worlds, meaning we have molecular control by choice of catalysts plus the robust crystalline nature of the COF,” says Christopher Chang, a chemist with Berkeley Lab’s Chemical Sciences Division, and a co-leader of this study. “To date, such porous materials have mainly been used for carbon capture and separation, but in showing they can also be used for carbon dioxide catalysis, our results open up a huge range of potential applications in catalysis and energy.” Chang and Omar Yaghi, a chemist with Berkeley Lab’s Materials Sciences Division who invented COFs, are the corresponding authors of a paper inScience that describes this research in detail. The paper is titled “Covalent organic frameworks comprising cobalt porphyrins for catalytic CO2 reduction in water.” Lead authors are Song Lin, Christian Diercks and Yue-Biao Zhang. Other co-authors are Nikolay Kornienko, Eva Nichols, Yingbo Zhao, Aubrey Paris, Dohyung Kim and Peidong Yang. Chang and Yaghi both hold appointments with the University of California (UC) Berkeley. Chang is also a Howard Hughes Medical Institute (HHMI) investigator. Yaghi is co-director of the Kavli Energy NanoScience Institute (Kavli-ENSI) at UC Berkeley. The notoriety of carbon dioxide for its impact on the atmosphere and global climate change has overshadowed its value as an abundant, renewable, nontoxic and nonflammable source of carbon for the manufacturing of widely used chemical products. With the reduction of atmospheric carbon dioxide emissions in mind, Yaghi and his research group at the University of Michigan in 2005 designed and developed the first COFs as a means of separating carbon dioxide from flue gases. A COF is a porous three-dimensional crystal consisting of a tightly folded, compact framework that features an extraordinarily large internal surface area — a COF the size of a sugar cube were it to be opened and unfolded would blanket a football field. The sponge-like quality of a COF’s vast internal surface area enables the system to absorb and store enormous quantities of targeted molecules, such as carbon dioxide. Now, through another technique developed by Yaghi, called “reticular chemistry,” which enables molecular systems to be “stitched” into netlike structures that are held together by strong chemical bonds, the Berkeley Lab researchers were able to embed the molecular backbone of COFs with a porphyrin catalyst, a ring-shaped organic molecule with a cobalt atom at its core. Porphyrins are electrical conductors that are especially proficient at transporting electrons to carbon dioxide. “A key feature of COFs is the ability to modify chemically active sites at will with molecular-level control by tuning the building blocks constituting a COF’s framework,” Yaghi says. “This affords a significant advantage over other solid-state catalysts where tuning the catalytic properties with that level of rational design remains a major challenge. Because the porphyrin COFs are stable in water, they can operate in aqueous electrolyte with high selectivity over competing water reduction reactions, an essential requirement for working with flue gas emissions.” In performance tests, the porphyrin COFs displayed exceptionally high catalytic activity — a turnover number up to 290,000, meaning one porphyrin COF can reduce 290,000 molecules of carbon dioxide to carbon monoxide every second. This represents a 60-fold increase over the catalytic activity of molecular cobalt porphyrin catalyst and places porphyrin COFs among the fastest and most efficient catalysts of all known carbon dioxide reduction agents. Furthermore, the research team believes there’s plenty of room for further improving porphyrin COF performances. “We’re now seeking to increase the number of electroactive cobalt centers and achieve lower over-potentials while maintaining high activity and selectivity for carbon dioxide reduction over proton reduction,” Chang says. “In addition we are working towards expanding the types of value-added carbon products that can be made using COFs and related frameworks.”

The digital game that could cure TB .


 

tb game

A unique collaboration between two Scottish universities has produced a digital game that fights tuberculosis.

A team of undergraduates from Abertay University in Dundee has created Sanitarium, a game that invites people to play doctor.

Using scarce resources they must treat as many TB patients as they can.

Behind the game lies a mathematical model developed at St Andrews University that uses data from human interactions to simulate a drug trial.

The data collected by the game could help deliver new drug treatments to the developing world quicker and cheaper than ever before.

Tuberculosis (TB) is a global killer that is increasingly resistant to antibiotics. The global TB Alliance has been formed to fight it.

Prof Stephen Gillespie, who holds the Sir James Black chair of medicine at St Andrews University, is part of that fight.

“For a lot of the poorer parts of the world it remains a common problem,” he says.

“There are about eight million new cases ever year and about two to three million deaths.”

Innovative approaches are called for. Which is why Professor Gillespie found himself issuing a brief to a group of third year computer game students at Abertay.

They call themselves Radication Games.

Their task: to develop a game about curing TB in a virtual world that could lead to the same thing happening in the real one.

Their first hurdle: to make a game people would actually want to play.

The team’s lead programmer James Warburton led me through it.

“The player is presented with a doctor screen – the doctor they’ll be playing,” he said.

“It gives them information about how many patients they’ve got to cure and how many patients are still in treatment.

“On the next screen they get presented with a world map which represents patients as red dots across the world.

“They’re given three mini-games which diagnose and treat the patient.”

New drugs

For lead artist Chris Box the task was to make the game attractive.

He says: “The medical world is quite a dry subject, so we wanted to make it kind of pop and interesting so that people would want to pick it up and grab it.

“That’s been the challenge.”

And has he risen to it?

He smiles: “I hope so. It’s been received well.”

For a typical third year student project, creating an engaging digital experience would be enough.

But Prof Gillespie wanted more than a game.

He says: “We’re in the fortunate situation now that we’re starting to see new drugs coming through for tuberculosis.

“But each clinical trial costs more than $50m and there may be 100 different combinations.

“We can’t afford to do that many clinical trials.

“So if we can have a virtual clinical trial that tests the hypothesis whether that will work, we can select a smaller number of studies that are really worth doing and worth investing in.”

That is why, behind the game, there lies a mathematical model.

It has been developed at St Andrews to simulate drug trials, to cut the cost and length of the real things.

Mathematical model

At Abertay the Sanitarium team, led by game producer John Brengman, took on the task of building a game around that life or death research.

“With the mathematical model we have analytics running in the background that basically takes all the information happening in the game,” he told me.

“And we can save that and segment that and give it to the scientists and doctors to look at later.

“But if they were to come up with a new treatment for tuberculosis and a new mathematical model, we could plug that into the game.

“We could get players around the world playing it. And then we could take that new dataset, compare it to the old dataset, and there you have a simulated drug trial.”

That’s because the people who play the game add a vital element to the theoretical model: themselves.

“The most difficult thing in a mathematical model is human behaviour,” Professor Gillespie says.

“We can use the people who’re playing the game to mimic that behaviour.”

Job satisfaction

For the team’s sound designer Mazen Magzoub project Sanitarium has a special resonance. He’s from Sudan.

“There isn’t enough medication,” he says.

“And even when there is enough medication the nature of living in Sudan does not allow the patient to continue (treatment) for the prescribed period.

“And that makes the tuberculosis bacteria tolerant towards that certain type of antibiotic.

“That’s basically the challenge in the developing world.”

The Radication Games team intend to stay together after they graduate to continue developing a project which brings with it a special kind of job satisfaction.

The success of most digital games is measured in money. For Sanitarium it’ll be in how many lives it saves.

And for Prof Gillespie, working with the games team has brought another more personal benefit.

He says: “They’re very, very talented in every respect as you can see from the game.

“Even more talented: they make my research seem cool.”

All the ways caffeine affects your body in one handy infographic .


No wonder we’re so addicted.

CaffeineInfographic small

Caffeine is the most widely used drug in the world, but most of us don’t really know or care exactly what goes on inside our bodies when we drink our morning cup of coffee. Obviously it help us wake up and focus, but caffeine actually has some much broader much broader, and in some cases, more surprising effects. This Business Insider infographic (high res version here) summarises them all for you, so that you can really appreciate how much your flat white does for you.

Watch the video. URL: https://youtu.be/0mgmayMSESI

Criminal Minds Are Different From Yours, Brain Scans Reveal


The latest neuroscience research is presenting intriguing evidence that the brains of certain kinds of criminals are different from those of the rest of the population.

While these findings could improve our understanding of criminal behavior, they also raise moral quandaries about whether and how society should use this knowledge to combat crime.

The criminal mind

In one recent study, scientists examined 21 people with antisocial personality disorder – a condition that characterizes many convicted criminals. Those with the disorder “typically have no regard for right and wrong. They may often violate the law and the rights of others,” according to the Mayo Clinic.

Brain scans of the antisocial people, compared with a control group of individuals without any mental disorders, showed on average an 18-percent reduction in the volume of the brain’s middle frontal gyrus, and a 9 percent reduction in the volume of the orbital frontal gyrus – two sections in the brain’s frontal lobe.

Another brain study, published in the September 2009 Archives of General Psychiatry, compared 27 psychopaths — people with severe antisocial personality disorder — to 32 non-psychopaths. In the psychopaths, the researchers observed deformations in another part of the brain called the amygdala, with the psychopaths showing a thinning of the outer layer of that region called the cortex and, on average, an 18-percent volume reduction in this part of brain.

“The amygdala is the seat of emotion. Psychopaths lack emotion. They lack empathy, remorse, guilt,” said research team member Adrian Raine, chair of the Department of Criminology at the University of Pennsylvania, at the annual meeting of the American Association for the Advancement of Science in Washington, D.C., last month.

University of Pennsylvania criminologist Adrian Raine
University of Pennsylvania criminologist Adrian Raine
Credit: U Penn

In addition to brain differences, people who end up being convicted for crimes often show behavioral differences compared with the rest of the population. One long-term study that Raine participated in followed 1,795 children born in two towns from ages 3 to 23. The study measured many aspects of these individuals’ growth and development, and found that 137 became criminal offenders.

One test on the participants at age 3 measured their response to fear – called fear conditioning – by associating a stimulus, such as a tone, with a punishment like an electric shock, and then measuring people’s involuntary physical responses through the skin upon hearing the tone.

In this case, the researchers found a distinct lack of fear conditioning in the 3-year-olds who would later become criminals. These findings were published in the January 2010 issue of the American Journal of Psychiatry.

Neurological base of crime

Overall, these studies and many more like them paint a picture of significant biological differences between people who commit serious crimes and people who do not. While not all people with antisocial personality disorder — or even all psychopaths — end up breaking the law, and not all criminals meet the criteria for these disorders, there is a marked correlation.

“There is a neuroscience basis in part to the cause of crime,” Raine said.

What’s more, as the study of 3-year-olds and other research have shown, many of these brain differences can be measured early on in life, long before a person might develop into actual psychopathic tendencies or commit a crime.

Criminologist Nathalie Fontaine of Indiana University studies the tendency toward being callous and unemotional (CU) in children between 7 and 12 years old. Children with these traits have been shown to have a higher risk of becoming psychopaths as adults.

“We’re not suggesting that some children are psychopaths, but CU traits can be used to identify a subgroup of children who are at risk,” Fontaine said.

Yet her research showed that these traits aren’t fixed, and can change in children as they grow. So if psychologists identify children with these risk factors early on, it may not be too late.

“We can still help them,” Fontaine said. “We can implement intervention to support and help children and their families, and we should.”

These brain scans of psychopaths show a deformation in the amygdala compared to non-psychopaths, from a study by Adrian Raine and colleagues.
These brain scans of psychopaths show a deformation in the amygdala compared to non-psychopaths, from a study by Adrian Raine and colleagues.
Credit: Yang et al./Archives of General Psychiatry

Neuroscientists’ understanding of the plasticity, or flexibility, of the brain called neurogenesis supports the idea that many of these brain differences are not fixed. [10 Things You Didn’t Know About the Brain]

“Brain research is showing us that neurogenesis can occur even into adulthood,” said psychologist Patricia Brennan of Emory University in Atlanta. “Biology isn’t destiny. There are many, many places you can intervene along that developmental pathway to change what’s happening in these children.”

Furthermore, criminal behavior is certainly not a fixed behavior.

Psychologist Dustin Pardini of the University of Pittsburgh Medical Center found that about four out of five kids who are delinquents as children do not continue to offend in adulthood.

Pardini has been researching the potential brain differences between people with a past criminal record who have stopped committing crimes, and those who continue criminal behavior. While both groups showed brain differences compared with non-criminals in the study, Pardini and his colleagues uncovered few brain differences between chronic offenders and so-called remitting offenders.

“Both groups showed similar results,” Pardini said. “None of these brain regions distinguish chronic and remitting offenders.”

Ethical quandaries

Yet even the idea of intervening to help children at risk of becoming criminals is ethically fraught.

“Do we put children in compulsory treatment when we’ve uncovered the risk factors?” asked Raine. “Well, who decides that? Will the state mandate compulsory residential treatment?”

What if surgical treatment methods are advanced, and there is an option to operate on children or adults with these brain risk factors? Many experts are extremely hesitant to advocate such an invasive and risky brain intervention — especially in children and in individuals who have not yet committed any crime.

Yet psychologists say such solutions are not the only way to intervene.

“You don’t have to do direct brain surgery to change the way the brain functions,” Brennan said. “You can do social interventions to change that.”

Fontaine’s studies, for example, suggest that kids who display callous and unemotional traits don’t respond as well to traditional parenting and punishment methods such as time-outs. Instead of punishing bad behavior, programs that emphasize rewarding good behavior with positive reinforcement seem to work better.

Raine and his colleagues are also testing whether children who take supplemental pills of omega-3 fatty acids — also known as fish oil — can show improvement. Because this nutrient is thought to be used in cell growth, neuroscientists suspect it can help brain cells grow larger, increase the size of axons (the part of neurons that conducts electrical impulses), and regulate brain cell function.

“We are brain scanning children before and after treatment with omega-3,” Raine said. “We are studying kids to see if it can reduce aggressive behavior and improve impaired brain areas. It’s a biological treatment, but it’s a relatively benign treatment that most people would accept.”

‘Slippery slope to Armageddon’

The field of neurocriminology also raises other philosophical quandaries, such as the question of whether revealing the role of brain abnormalities in crime reduces a person’s responsibility for his or her own actions.

“Psychopaths know right and wrong cognitively, but don’t have a feeling for what’s right and wrong,” Raine said. “Did they ask to have an amygdala that wasn’t as well functioning as other individuals’? Should we be punishing psychopaths as harshly as we do?”

Because the brain of a psychopath is compromised, Raine said, one could argue that they don’t have full responsibility for their actions. That — in effect — it’s not their fault.

In fact, that reasoning has been argued in a court of law. Raine recounted a case he consulted on, of a man named Herbert Weinstein who had killed his wife. Brain scans subsequently revealed a large cyst in the frontal cortex of Weinstein’s brain, showing that his cognitive abilities were significantly compromised.

The scans were used to strike a plea bargain in which Weinstein’s sentence was reduced to only 11 years in prison.

“Imaging was used to reduce his culpability, to reduce his responsibility,” Raine said. “Yet is that not a slippery slope to Armageddon where there’s no responsibility in society?”

Age and Anesthesia


Image: iStockImage: iStock

Recent Massachusetts General Hospital investigations into the neurobiology underlying the effects of general anesthesia have begun to reveal the ways different anesthetic agents alter specific aspects of the brain’s electrical signals, reflected by electroencephalogram signatures.

While those studies have provided information that may lead to improved techniques for monitoring the consciousness of patients receiving general anesthesia, until now they have been conducted in relatively young adult patients.

Now a series of papers from Harvard Medical School researchers at Mass General is detailing the differences in the way common anesthetics affect the brains of older patients and children, findings that could lead to ways of improving monitoring technology and the safety of general anesthesia for such patients.

“Anesthesiologists know well that the management of patients age 60 or older requires different approaches than for younger patients,” said Emery Brown, the Warren M. Zapol Professor of Anæsthesia at Mass General. “The doses required to achieve the same anesthetic state in older patients can be as little as half what is needed for younger patients. Explanations for that difference have focused on age-related declines in cardiovascular, respiratory, liver and kidney function, but the primary sites of anesthetic effects are the brain and central nervous system.”

Patrick Purdon, HMS assistant professor of anæsthesia at Mass General, added, “We know even less about how anesthetic drugs influence brain activity in children, and the current standard of care for assessing the brain state of children under anesthesia calls only for monitoring vital signs like heart rate and blood pressure. This lack of knowledge is especially troubling, given recent studies suggesting an association between early childhood surgery requiring general anesthesia and later cognitive problems.”

EEG signatures

Brown and Purdon led a Mass General research team investigating the neural mechanisms of general anesthesia that identified EEG signatures indicating when patients lose and regain consciousness and the EEG patterns—called oscillations—produced by specific drugs while patients are unconscious.

In young adults, anesthesia-induced unconsciousness is associated with medium frequency (around 10 Hz) EEG oscillations called frontal alpha waves that are highly synchronized between the cerebral cortex and thalamus, a pattern that is believed to block communication between those brain structures.

Two papers from the Mass General team recently published in the British Journal of Anæsthesia are the first to take a detailed look at anesthesia-induced brain changes in older patients. Purdon and Brown are co-corresponding authors ofone study that analyzed detailed EEG recordings of 155 patients aged 18 to 90 receiving either propofol or sevoflurane.

That study found that the EEG oscillations of older patients were two to three times smaller than those of younger adults with reduced occurrence of frontal alpha waves. The synchronization between the cortex and thalamus occurred at slightly lower frequencies in older patients, who were more likely than younger patients to experience a state called burst suppression that reflects profoundly deep anesthesia at lower doses.

Recovery

The other BJA study, led by Ken Solt, HMS associate professor of anaesthesia at Mass General, found that older animals took two to five times longer than younger animals to recover from equal anesthetic doses and observed similar age-related differences in EEG patterns as seen in the patients.

Another study appearing in the same issue of the British Journal of Anæsthesia —co-authored by Purdon—analyzed EEG patterns of 54 patients ranging from infancy through age 28 during anesthesia with sevoflurane. They found that anesthesia-induced EEG signals tripled in power from infancy until around age 6 and then dropped off to the typical young-adult level at around age 20.

Frontal alpha waves were not observed in children under the age of 1, suggesting that the brain circuits required for cortical/thalamic synchronization had not yet developed. Purdon and Brown were also co-authors of aneLife study led by Boston Children’s Hospital investigatorsLaura Cornelissen, HMS research fellow in anesthesia, and Charles Berde, HMS professor of anaesthesia (pediatrics), that detailed the EEG activity of infants 6 months and younger, showing how their patterns evolved toward those more typical of adults over just a few months.

“It appears as though the structure of anesthesia-induced brain dynamics mirrors brain development in children, with different brain wave patterns ‘turning on’ at ages that coincide with known developmental milestones,” said Purdon. “In older patients we see a similar effect but in reverse, with certain brain waves decaying in a manner consistent with brain aging.”

Monitoring

It has been known that commercially available EEG-based anesthesia monitors were developed for young adults, Purdon said, and while they are limited for that population—reducing brain activity to a single number—they are even more inaccurate for children and the elderly.

“These studies illustrate why this is the case and suggest a new, age-specific monitoring paradigm that—along with monitors that track a broader range of EEG signals—could help avoid both anesthesia-induced neurotoxicity in children and postoperative delirium and cognitive dysfunction in elderly patients,” Purdon said.

Brown added, “Understanding how the brain’s responses to anesthesia change with age allows us to provide personalized, patient-specific strategies for monitoring the brain and dosing the anesthetics, thereby moving us closer to side-effect free anesthesia care.

Unpacking the Epigenetics of Cancer.


 

  • Researchers at the University of Iowa studied how PHD finger protein 1 (PHF1) binds to histone H3 trime- thylated at Lys36 (H3K36me3). They found that PHF1’s Tudor domain (light purple) binds to the histone’s methylated tail (pink). Note that the aromatic residues of the Tudor domain that constitute the methyl-lysine binding pocket are highlighted in blue. [Image courtesy of Catherine A. Musselman, Ph.D.]

    Chromatin-associated factors play an important role in the epigenetic regulation of gene expression. These factors include various proteins that contribute to chemical alteration of DNA or histones, as well as those that control chromatin structure at the nucleosome level.

    Extensive studies have documented chromosomal aberrations and dysregulation of chromatin factor gene expression in many types of cancer. A single defect in a chromatin factor can potentially affect the expression patterns of several hundred target genes, resulting in the disruption of multiple cellular pathways.

    As further research into chromatin factors provides an increasing level of detail regarding their interactions with multiple targets, cancer epigenetics is emerging as a rapidly developing area of research. As a result, the dysregulation of chromatin factor gene expression offers attractive opportunities for the development of therapeutic agents.

    The topic will be highlighted at Chromatin and Epigenetics in Cancer, an American Association for Cancer Research (AACR) conference that will be held September 24–27 in Atlanta. Cancer epigenetics has also been discussed at meetings that were more application oriented, such as CHI’s Epigenetic Inhibitor Discovery conference held earlier this year in San Diego.

    “Histone modifications can alter chromatin in two ways,” says Catherine A. Musselman, Ph.D., assistant professor of biochemistry at the University of Iowa, Carver College of Medicine. “They may directly alter chromatin contacts, or they may indirectly remodel the structure.”

    Direct mechanisms involve changes at histone-histone or histone-DNA contacts that affect chromatin conformation. One common modification is acetylation of lysine residues in histones, which neutralizes their positive charge and disrupts their electrostatic interactions with other proteins. Indirect effects involve chromatin remodeling cofactors, whose interaction with specifically modified histones can recruit them to certain regions of chromatin, for example, during the transcription process.

    Dr. Musselman’s group studies histone lysine methylation, one of the most diverse histone modifications. It can have a variety of functional effects. “For instance, trimethylation of histone H3 at Lys4 (H3K4me3) is a marker of promoters of transcriptionally active genes,” notes Dr. Musselman. In contrast, trimethylation of lysine 27 (H3K27me3) is typically associated with gene repression.

    In particular, Dr. Musselman’s research focuses on a class of proteins known as plant homeodomain  (PHD) finger proteins. PHD finger protein 1 (PHF1) is an essential component of  nuclear protein complexes like the transcriptional repressor polycomb repressive complex 2 (PRC2), as well as the DNA damage repair enzymes Ku70/Ku80.

    “Dysregulation of PHF1 alters global H3K27me3 levels, which leads to altered gene expression levels,” explains Dr. Musselman. The exact effects are gene-dependent; however, the importance of PHF1 to the DNA damage response pathway, as well as its reported involvement in p53-mediated pathways, suggest that it has multiple roles in tumorigenesis.

  • Interactions with RNA Polymerase II

    Brian Strahl, Ph.D., a professor of biochemistry and biophysics at the University of North Carolina School of Medicine, is addressing several intriguing issues that surround the mechanisms by which distinct chromatin structures are established and maintained, as well as how the underlying DNA is made accessible to the transcriptional machinery. Much of his research centers on the properties of the yeast transcription factor Set2 and the human equivalent, SETD2.

    “Set2/SETD2 is a histone methyltransferase I first identified as a postdoctoral fellow,” says Dr. Strahl. At the time, little was known about the role of histone methylases in chromatin function. “By tethering Set2 to gene promoters, I was able to initially show that Set2 and its methylation in yeast cells had the ability to turn off transcription,” he adds.

    Although Set2 has been extensively studied in yeast, the role of SETD2 in humans is less clear. Like Set2, SETD2 appears to associate with RNA polymerase II during transcription to trimethylate the lysine-36 residue in histone H3 (H3K36me3). This process is a key factor in the response to double-stranded breaks (DSBs) in DNA, a phenomenon observed in multiple types of cancer. SETD2 is one of the most frequently mutated proteins in cancer. “The frequency of mutation is especially high in bladder, breast, gliomas and most significantly, kidney cells,” explains Dr. Strahl.

    The question of how RNA polymerase II senses and responds to DNA damage in cancer remains unanswered. One possibility is that it pauses at the site of DSBs. “At that point,” notes Dr. Strahl, “repair machinery coupled with the polymerase, along with DNA damage response machinery, would then take action.” Future research in Dr. Strahl’s laboratory will explore the question of how SETD2 loss of function may result in inappropriately repaired DNA and genomic instability—a characteristic of many cancer types.

  • Jumonji Family of Demethylases

    Histone methylation of lysine and arginine residues, especially trimethylation, was long considered to be irreversible. However, recent research has shown that the “erasing” of histone methyl marks by a group of demethylase enzymes also plays a significant role in epigenetic regulation of gene transcription.

    Kristian Helin, Ph.D., director and professor at the Biotech Research & Innovation Centre (BRIC), University of Copenhagen, studies a class of demethylases known as Jumonji (JmjC) proteins. “JmjC-containing histone demethylases can reverse the effect of histone methyltransferases, but in general they do not appear to be regulators of transcription,” says Dr. Helin. Instead, these proteins stabilize the transcriptional complexes formed by transcription factors and other proteins involved in cell signaling pathways.

    One member of the JmjC family, UTX, is a demethylase specific to H3K27me3/me2 modifications. In vivo, UTX cooperates with the histone methyltransferase MLL4; these proteins are part of a complex that act as a transcriptional activator. Mutations in the gene encoding UTX are associated with “many different types of cancer including renal cell carcinomas, leukemia, and other hematopoietic cancers,” according to Dr. Helin.

    Future research in Dr. Helin’s group will use genetically engineered mouse models to assess the roles of specific histone-modifying enzymes in cancer. The goal, declares Dr. Helin, is “elucidation of how these enzymes contribute to normal proliferation and development, and how their deregulation leads to cancer.”

  • Inhibitors of Jumonji Enzyme Activity

    Click Image To Enlarge +
    At the University of Texas Southwestern Medical Center, researchers focus on the role of Jumonji histone demethylases in cancer. This image, prepared by Juan Bayo-Fina, Ph.D., depicts various means by which histone epigenetic marks may be added or removed. [Image courtesy of the Martinez Lab]

    JmjC demethylases also constitute the primary area of research for Elisabeth D. Martinez, Ph.D., an assistant professor of pharmacology at the University of Texas Southwestern Medical Center. “In cancer,” says Dr. Martinez, “the expression of some histone demethylases is highly increased, and this hyperactivity leads to aberrant gene expression and defects in the normal regulation of growth pathways.”

    Dr. Martinez is investigating the therapeutic potential of a small molecule drug candidate known as JIB-04. “In biochemical assays using recombinant Jumonji enzymes, JIB-04 inhibits their histone demethylase activity,” explains Dr. Martinez. Her studies also showed that JIB-04 inhibited histone demethylase activity on H3K9me3 in lysates of cancer cells but not in patient-matched normal cells.

    While further studies will provide mechanistic details, Dr. Martinez suggests that “JIB-04 blocks tumor growth and prolongs survival by reprogramming the tumor’s transcriptional profile,” and that the process is mediated, in part, by the drug’s effects on Jumonji demethylase activity.

    Other researchers have studied different classes of histone demethylases inhibitors, including alpha-ketoglutarate analogs. Compared to these compounds, however, JIB-04 is cell-permeable and has better efficacy in the mouse models tested. “In addition, data to date demonstrate that it is markedly more specific than alpha-ketoglutarate analogs and inhibits Jumonji demethylases but not other cellular alpha-ketoglutarate–dependent enzymes,” observes Dr. Martinez.

  • Clinical Trials

    Several companies are targeting histone modification pathways in efforts to bring new drugs to the market for cancer therapy. One such company is Cambridge-based Constellation Pharmaceuticals. The company recently announced the initiation of a Phase I trial of a compound known as CPI-1205, which targets pathways mediated by the protein Enhancer of Zeste Homolog 2 (EZH2).

    “EZH2 functions as the catalytic component of the multisubunit complex PRC2,” says Robert Sims, executive director of biology at Constellation. “This complex functions in the maintenance of gene silencing, in part due to the ability of EZH2 to methylate H3K27.”

    Sims explains that mutations in the EZH2 gene that alter its substrate specificity have been associated with several non-Hodgkin lymphoma subtypes (including diffuse large B-cell lymphoma and follicular lymphoma) and melanoma. He adds that “CPI-1205 inhibits the EZH2 methyltransferase activity, and thus impedes EZH2’s potential to repress gene expression in lymphoma.”

    Constellation is also evaluating other inhibitors, including one that targets the bromodomain and extra-C terminal domain (BET) family of chromatin adaptors. These proteins “bridge” transcriptional coactivators to acetylated histones during a late stage of the transcription cycle, typically at transcriptional pausing of RNA polymerase II. Dysregulation of BET gene expression is linked to NUT midline carcinoma, a rare, aggressive epithelial cancer characterized by a chromosomal translocation in the nuclear protein in testis (NUT) gene.

    “Many additional cancers utilize BET proteins to drive oncogenic gene expression, such as MYC, MYB, and BCL-2,” notes Sims. These cancers include leukemia, lymphoma, multiple myeloma, and neuroblastoma.

    Constellation is actively pursuing research in other chromatin-modifying pathways, including reversible lysine methylation and acetylation. “This includes all aspects of these signaling pathways—writing, erasing, and reading,” asserts Sims. He also indicates that the company is exploring other aspects of chromatin structure and function, with an emphasis on modulating gene regulatory circuits.

Scientists are working on rechargeable batteries with almost infinite lifetimes .


Researchers in the US have been working with Samsung to develop a new type of rechargeable battery that can be sustained through “hundreds of thousands” of charge cycles, and has up to 30 percent more energy density – a measure of energy per unit volume – than today’s batteries.

The key was figuring out how to use a solid electrolyte in their new batteries, instead of relying on the liquid electrolyte that’s used in today’s rechargeable lithium-ion batteries. Not only can their solid-state electrolytes support a greater lifespan for the battery while also boosting the amount of power it can store, it’s also safer than its liquid counterpart, which has been known to overheat and explode on occasion.

The lithium-ion rechargeable batteries that power our smartphones, laptops, e-cigarettes, and hybrid cars all run on a liquid solvent that’s responsible for transferring charged particles from one electrode to the other during charging and discharging cycles.

The problem is that this process can cause the liquid to overheat and combust, causing potentially dangerous situations such as when Boeing’s entire fleet of 787 Dreamliner jets were temporarily grounded in 2013 because electrolyte had leaked from lithium ion batteries onto the interior of one plane’s fuselage.

Solid-state electrolyte, on the other hand, brings with it no such complications. “You could throw it against the wall, drive a nail through it – there’s nothing there to burn,” one of the team, Gerbrand Ceder from the Massachusetts Institute of Technology (MIT), said in a press release. He says it creates “almost a perfect battery, solving most of the remaining issues” in battery lifetime, safety, and cost, with “virtually no degradation reactions left”. This means it will last through more charging cycles than you’re ever likely to need.

While Cedar’s team isn’t the first to pursue the solid-state electrolyte, it’s the first to figure out how to make it work in a battery that’s powerful enough to not only challenge today’s technology, but overtake it. “There was a view that solids cannot conduct fast enough,” he says. “That paradigm has been overthrown.”

The researchers used a class of materials known as superionic lithium-ion conductors – compounds of lithium, germanium, phosphorus, and sulphur – to produce the electrolyte, and report in Nature Materials that they conduct the charged particles fast enough to be used in a commercial battery, and can operate at much colder temperatures than conventional lithium-ion batteries: up to –28 degrees Celsius.

Hopefully by partnering with tech giant Samsung, the team will have the help it needs to put this kind of technology on the market in the years to come. Because it’s 2015 and we still haven’t figured out how to free ourselves from the nightly phone charge.