Thursday, December 14, 2017

We Told You Facebook Is Evil - Damn Near As Evil As Weed

WaPo |  Chamath Palihapitiya began working for Facebook in 2007 and left in 2011 as its vice president for user growth. When he started, he said, there was not much thought given to the long-term negative consequences of developing such a platform.

“I think in the back, deep, deep recesses of our minds, we kind of knew something bad could happen,” said Palihapitiya, 41. “But I think the way we defined it was not like this.”

 That changed as Facebook’s popularity exploded, he said. To date, the social network has more than 2 billion monthly users around the world and continues to grow.

But the ability to connect and share information so quickly — as well as the instant gratification people give and receive over their posts — has resulted in some negative consequences, according to Palihapitiya.

“It literally is a point now where I think we have created tools that are ripping apart the social fabric of how society works. That is truly where we are,” he said. “The short-term, dopamine-driven feedback loops that we have created are destroying how society works: no civil discourse, no cooperation, misinformation, mistruth. And it’s not an American problem. This is not about Russian ads. This is a global problem.”

Facebook has pushed back on the former executive’s comments, saying in a statement Tuesday that Palihapitiya has not worked there for more than six years and that it was “a very different company back then.”

Monday, November 6, 2017

Opioid Crisis: Nobody is Talking About Sugar

theconversation |  Could a diet high in refined sugars make children and adults more susceptible to opioid addiction and overdose? New research, from our laboratory of behavioral neuroscience at the University of Guelph, suggests it could. 

Nobody is talking about sugar. 

And yet there is substantial experimental evidence that refined sugar can promote addictive behaviours by activating the brain’s rewards centres in much the same way as addictive drugs. Opioid abuse is also associated with poor dietary habits, including preferences for sugar-rich foods, as well as malnutrition. These connections have led to questions of whether excessive consumption of refined sugar may affect vulnerability to opioid addiction. 

To explore the possible role of a sugar-rich diet in opioid addiction, we investigated whether unlimited access to high fructose corn syrup (HFCS) altered rats’ neural and behavioural responses to the semi-synthetic opioid, oxycodone. 

Our findings suggest that a diet high in corn syrup may dampen the reward associated with oxycodone and may therefore encourage consumption of higher quantities of the drug.  Fist tap Dale.

Tuesday, October 24, 2017

Engineering $$Billion Behavioral Addictions

medium |  Yin asked not to be identified by her real name. A young addict in her mid-twenties, she lives in Palo Alto and, despite her addiction, attends Stanford University.

She has all the composure and polish you’d expect of a student at a prestigious school, yet she succumbs to her habit throughout the day. She can’t help it; she’s compulsively hooked.

Yin is an Instagram addict. The photo sharing social network, recently purchased by Facebook for $1 billion, captured the minds of Yin and 40 million others like her.

The acquisition demonstrates the increasing importance–and immense value created by–habit-forming technologies. Of course, the Instagram purchase price was driven by a host of factors including a rumored bidding war for the company.

But at its core, Instagram is the latest example of an enterprising team, conversant in psychology as much as technology, that unleashed an addictive product on users who made it part of their daily routines.

Like all addicts, Yin doesn’t realize she’s hooked. “It’s just fun,” she says as she captures her latest in a collection of moody snapshots reminiscent of the late 1970s. “I don’t have a problem or anything.
I just use it whenever I see something cool. I feel I need to grab it before it’s gone.”

Monday, October 9, 2017

The Brain's Lymphatic System

theatlantic  |  Reich started his search in 2015, after a major study in Nature reported a similar conduit for lymph in mice. The University of Virginia team wrote at the time, “The discovery of the central-nervous-system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology.” The study was regarded as a potential breakthrough in understanding how neurodegenerative disease is associated with the immune system.

Around the same time, researchers discovered fluid in the brains of mice and humans that would become known as the “glymphatic system.” It was described by a team at the University of Rochester in 2015 as not just the brain’s “waste-clearance system,” but as potentially helping fuel the brain by transporting glucose, lipids, amino acids, and neurotransmitters. Although since “the central nervous system completely lacks conventional lymphatic vessels,” the researchers wrote at the time, it remained unclear how this fluid communicated with the rest of the body.

Reich reasoned that since this fluid exists in human brains, and the conduits exist in mice, the conduits likely exist in humans, too. After two years of work and inordinately complex physics calculations, Reich’s team found the vessels. When Reich started telling colleagues what his team found, he got two reactions: “No way, it’s not true,” and “Yeah, we’ve known that.”

There are occasional references to the idea of a lymphatic system in the brain in historic literature. Two centuries ago, the anatomist Paolo Mascagni made full-body models of the lymphatic system that included the brain, though this was dismissed as an error. A historical account in The Lancet in 2003 read: “Mascagni was probably so impressed with the lymphatic system that he saw lymph vessels even where they did not exist—in the brain.”

No one had published definitive evidence of lymph vessels in any brain until the Virginia mouse study and a concordant Helsinki one in 2015. “You could say that was the discovery,” Reich said. “Did Newton discover gravity? I mean—not to equate these two discoveries—but obviously people knew that things fell before Newton’s apple.”

His team’s discovery, though, not only shows that the vessels exist in people, but just how elaborate the system is.

Tuesday, October 3, 2017

Las Vegas Mass Shooting's Point of Commonality?

theduran |  Until governments such as that of the United States, cracks down on big pharmaceutical companies, black-market drug dealers and the deep state’s involvement in narcotics trafficking, things will only get worse. It is no coincidence that the number of mass shootings as well as cruel and usual homicides have increased in-line with the use of psychotropic drugs.

Furthermore, society must work diligently to stigmatise drug use until such a point where being a drug addict is socially derided to the same degree as being a member of a known terrorist organisation.

The following is a list compiled by WND news, detailing the mass shooters and other obviously insane killers, known to be taking psychotropic drugs prior to or during their killing sprees:

Monday, September 18, 2017

think i've figured out my nearly complete dislike of cats (and the completely irrational liking by others)

Nature | Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer

[Ed: to view the entire report, install the Unpaywall extension]

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: “Orbital-deconvolution” elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. “Cluster-deconvolution” revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, “disease-deconvolution” identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer’s disease, and cancer. This “reconstruction-deconvolution” logic provides templates of progenitor cells’ potentiating effects, and components affecting human brain parasitism and diseases.

Tuesday, August 8, 2017

Impossible Burgers

NYTimes |  One of the chief selling points of the Impossible Burger, a much ballyhooed plant-based burger patty, is its resemblance to meat, right down to the taste and beeflike “blood.”

Those qualities, from an ingredient produced by a genetically engineered yeast, have made the burger a darling among high-end restaurants like Momofuku Nishi in New York and Jardinière in San Francisco, and have attracted more than $250 million in investment for the company behind it, Impossible Foods.

Now, its secret sauce — soy leghemoglobin, a substance found in nature in the roots of soybean plants that the company makes in its laboratory — has raised regulatory questions.

Impossible Foods wants the Food and Drug Administration to confirm that the ingredient is safe to eat. But the agency has expressed concern that it has never been consumed by humans and may be an allergen, according to documents obtained under a Freedom of Information request by the ETC Group as well as other environmental and consumer organizations and shared with The New York Times.

“F.D.A. believes the arguments presented, individually and collectively, do not establish the safety of soy leghemoglobin for consumption,” agency officials wrote in a memo they prepared for a phone conversation with the company on Aug. 3, 2015, “nor do they point to a general recognition of safety.”

Tuesday, July 11, 2017

Cannabinoids and Inflammation Webinar

thescientist |  FREE Webinar
Thursday, September 28, 2017
2:30 - 4:00 PM EDT
Simmering, low-level inflammation throughout the body is responsible for many disease processes, ranging from osteoarthritis and cardiovascular disease, to digestive disorders and neurodegeneration. The bioactive molecules, known as cannabinoids, found in plants of the Cannabis species, have been shown to possess powerful anti-inflammatory attributes, and research into their mechanisms of action, efficacy, and tolerability are underway. To explore the potential for cannabinoid-based and/or endocannabinoid-targeted therapeutics in the realm of human disease, and particularly diseases with an inflammatory component, The Scientist is bringing together a panel of experts to discuss their research, and to offer insight into the rewards and challenges of studying a biomedical application for a well-known, but controlled, substance. Attendees will have the opportunity to interact with the experts, ask questions, and seek advice on topics related to their research.
Topics to be covered:
  • Exogenous and endogenous cannabinoid mechanisms of action in the setting of inflammatory disease
  • Targeting the endocannabinoid system for therapeutic effects

Meet the Speakers:

Anton Reiner, PhD
Professor, Department of Anatomy and Neurobiology
University of Tennessee Health Science Center
Yannick Marchalant, PhD
Assistant Professor, Departments of Psychology and Neuroscience
Central Michigan University

Tuesday, June 13, 2017

Celiac Far More Prevalent

thescientist |  In 2015, gastroenterologist Edwin Liu set to work on a clinical and genetic data set that had been growing for more than 20 years. The data pertained to celiac disease, a lifelong condition involving bouts of severe gastrointestinal distress and other symptoms, triggered by ingestion of gluten proteins that are found in wheat and several other grains. In a two-decade collaboration with researchers at Children’s Hospital Colorado in Denver, Liu’s predecessors and colleagues at the University of Colorado kept track of 1,339 babies born in the city who were deemed at risk of developing the disease due to mutations in celiac-linked genes. The researchers carried out yearly tests to see whether or not the children developed the disease, hoping to better define the risk associated with each of the genetic variants.

Not far into his analyses, however, Liu found something in the data that undermined a much larger assumption in the celiac field. “Usually, when we quote numbers for celiac disease, we’re quoting around 1 percent” prevalence in the US population, he says. But using data from this cohort along with estimated frequencies of each genotype across the Denver metro area to extrapolate the incidence of celiac disease to the general population, Liu found that the true prevalence of celiac disease had to be much greater—more than 3 percent by age 15. “It was a surprise,” he says. “These numbers are much higher than anything else quoted in the U.S.”

Researchers reading the paper, which was published online earlier this year in Gastroenterology,1 were similarly taken aback. “If you look at the rates, it’s frightening,” says Joseph Murray, a celiac researcher at the Mayo Clinic in Rochester, Minnesota. Of course, the statistic could be specific to the Denver cohort, he notes, but it does fit in with similar trends reported both in the U.S. and around the world.

Celiac symptoms, which include abdominal pain and distension, diarrhea and flatulence, nausea, and fatigue, are brought on by ingestion of gluten—a protein complex present in wheat, barley, and rye. Unlike food allergies, which are often primarily mediated by an overreaction of adaptive immune responses such as immunoglobulin E antibody production and mast cell activation, celiac disease engages both innate and adaptive immune pathways, and produces antibodies that target not only gluten, but the body’s own proteins. As a result, the disease is generally considered an autoimmune condition. (See illustration.) Triggered by even tiny amounts of gluten, these immunological attacks lead to T cell–mediated atrophy of the gut wall, which can be characterized via a biopsy of the small intestine for celiac diagnosis (see “Diagnosing Celiac Disease”).

As the use of biopsy and other diagnostic methods have improved in recent decades, celiac disease has become easier to detect. So when the first reports of increasing numbers of celiac cases in the U.S. came out in the early 2000s, many researchers attributed the uptick to progress in disease recognition. But closer scrutiny of the data suggested there was more going on. “We weren’t just better at finding celiac disease,” Murray says. “There was a lot more of it to go around.”

Wednesday, April 12, 2017

Chronotherapy: Another Compelling Case for Evidence-Based, Data-Driven Medicine

thescientist |  For three consecutive winters, starting in 2011, researchers at the University of Birmingham asked healthy men and women over the age of 65 to come in to clinics across the western Midlands in the U.K. for a seasonal influenza vaccination at specific times of day—either between 9 and 11 a.m., or between 3 and 5 p.m. Blood drawn a month later revealed that participants, who totaled nearly 300 over the three years, had higher levels of anti-flu antibodies if they’d received their vaccinations in the morning.1 The results suggested that daily rhythms of people’s bodies tweaked the vaccine’s effectiveness. Lead author Anna Phillips Whittaker had suspected as much, after observing similar trends in her studies on behavioral factors such as exercise that affect vaccination responses, and in the wake of a growing body of literature suggesting that a little timing can go a long way when it comes to health.

Many hormones and immune signals are produced rhythmically in 24-hour cycles. Cortisol, for example, which is known to suppress inflammation and regulate certain T cell–mediated immune responses, peaks early in the morning and ebbs as the day progresses. Other facets of the immune system undergo similar cycles that could underlie the differences in antibody responses Phillips observed among people receiving the flu vaccine. Much more work is required to nail down the immune mechanisms responsible for such variation and exploit them appropriately, she says. But timing flu vaccine delivery would be straightforward to implement. “It’s such a simple, low-risk intervention that’s free to do, and could have massive implications for vulnerable populations.”

Across diseases, from cancer and cardiac ailments to allergies and arthritis, epidemiological data and clinical trials are revealing that timing medications to the body’s internal clock could improve their effectiveness and reduce side effects. Although this concept, known as chronotherapy, has existed for at least 60 years, it has received little attention from physicians. But as biologists continue to unveil the molecular intricacies of cellular rhythms, they are beginning to realize just how pervasive the circadian clock’s influence is. In a 2014 study of gene expression in mice, for example, researchers found periodic expression in conserved mammalian genes targeted by 56 of the top 100 best-selling drugs in the U.S., including aripiprazole (Abilify, an antipsychotic), esomeprazole (Nexium, for heartburn), and duloxetine (Cymbalta, for depression), even though most are not currently prescribed with suggested dosing times.2

But chronotherapy is gaining clinical traction, says University of Pennsylvania chronobiologist John Hogenesch, senior author on the 2014 study. “Now we have the groundwork to precisely understand a person’s clock and leverage that information for better health,” he says. “Because of the molecular work, we’ve opened new doors here. This [idea] is not coming from left field anymore.”

Even so, researchers and clinicians working on chronotherapy still face skepticism, and implementing a new drug-delivery protocol or gaining regulatory approval from the US Food and Drug Administration (FDA) for time-of-day indications remains challenging. Thus, while the biomedical research community is starting to take notice of the body’s internal rhythms, timed therapies are still the exception to the rule.

Friday, March 24, 2017

Molecular Oncology: Accept No Substitutes

Telegraph |  Two thirds of cancers are unavoidable even if you live a healthy life, a study has shown.
Scientists in the US found cancers are caused by random mistakes in the genetic code that occur when cells divide.

The findings challenge the widespread view that cancer mutations are generally inherited or triggered by environmental factors.  Instead, the vast majority of cancers are probably down to unlucky defects in replicating DNA that occur out of the blue, they suggest.

Lead scientist Dr Cristian Tomasetti, from Johns Hopkins Kimmel Cancer Center in the US, said: "It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer.

"But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes.

"These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes."

The research, published in the journal Science, indicates that almost two-thirds of cancer-causing mutations are due to DNA copying errors.

Tuesday, March 21, 2017

Obesity, Toxic Fat. Diabetes - What If Our Current Understanding Is All Wrong?

theatlantic |  Scott was not named for the Scott Summers of Marvel fame (more commonly known as Cyclops), but this was the analogous origin story of a scientist. His father’s diagnosis was Scott’s transformative moment—his spider bite, radiation blast, or, in the case of Cyclops, attack of his family’s spacecraft by the interstellar Shi’ar Empire. And unlike some children who promise to cure their parents but then go into finance or real estate, Summers actually went to graduate school and got a Ph.D. in physiology.

When Scott left the Midwest to work in a lab at the University of Pennsylvania, he got his first insight toward a hypothesis that he believes could revolutionize our understanding of human metabolism and disease—and could help explain why skinny people aren’t necessarily metabolically healthy, or vice versa.

“We now know that both lean and obese individuals are susceptible to diabetes,” Summers, now the chair of nutrition and integrative physiology at the University of Utah, explained to me. “We think it’s basically because of their lipid compositions, and the accumulation of one type in particular—called ceramides—that might be increasing susceptibility of people to diabetes.”

At the heart of this idea is the model that says obesity is associated with diabetes and heart disease because all three are due to an error in the way the body stores energy. We carry most fat as triglycerides in adipose (“fat”) cells, which contain tremendous amounts of energy.

“That’s a pretty safe way to store it,” Summers explains. At least, it’s not necessarily unhealthy to have this type of fat. “But some of that stored fat can actually spill out into another pathway and give rise to ceramides. We think those tend to be pretty toxic.”

Ceramides are a family of waxy lipids that have even been called “toxic fat,” as they were in the press release for Summers’s latest study in the journal Cell Metabolism. The researcher Bhagirath Chaurasia, who works with Summers, clarified that “toxic fat” is an accurate, non-sensational term, in that ceramides are involved in the process of lipotoxicity. That is, they cause dysfunction in other lipids. Because in addition to storing triglycerides, adipose cells also help the body sense its nutritional status by secreting compounds that communicate with other cells. Among those signals are ceramides, and alterations in this process seem to be at the root of much metabolic disease.

Saturday, February 18, 2017

Broad Wins CRISPR Patent Interference Case

thescientist  |   US Patent and Trademark Office’s Patent Trial and Appeal Board (PTAB) today (February 15) issued a ruling on a patent dispute regarding CRISPR gene editing. The judges declared that the work by Jennifer Doudna of the University of California, Berkeley, and colleagues (including Emmanuelle Charpentier, then at the University of Vienna) does not directly compete with the work of Feng Zhang at the Broad Institute of MIT and Harvard, which was granted the original CRISPR patent in April 2014.
“Broad has persuaded us that the parties claim patentably distinct subject matter,” the court wrote in its 51-page decision (which accompanied its two-page order). “Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment.”
“It looks like Broad has the decisive victory in this case,” Jake Sherkow of New York Law School told The Scientist.
UC Berkeley said that, while it “respects” today’s ruling and is “pleased” that its patent application can now move forward, the university is considering “all options for possible next steps in this legal process, including the possibility of an appeal of the PTAB’s decision,” a statement read. “We continue to maintain that the evidence overwhelmingly supports our position that the Doudna/Charpentier team was the first group to invent this technology for use in all settings and all cell types.”
If UC Berkeley does appeal to the US Court of Appeals for the Federal Circuit, “those cases take roughly a year from soup to nuts,” said Sherkow. In that circumstance, a decision would likely come from the appellate court “sometime in February or March of next year.”

Monday, January 23, 2017

The Role of Bioactive Lipids in Cancer Metastasis

thescientist | Although metastasis is the leading cause of death among people with cancer, for the most part, researchers are stumped about which molecular signals allow malignant cells to leave primary tumors and start new ones. Two studies published in Nature this month highlight roles in metastasis for an unexpected group of molecules—lipids.
“For many years, we were studying peptides and proteins,” said Mariusz Ratajczak, a cell biologist at the University of Louisville who was not involved in the studies. “Now we are coming to bioactive lipids.”
In the first study, published January 5, researchers at the Institute for Research in Biomedicine (IRB) in Barcelona reported that, in mice, human oral cancer cells that are most likely to migrate from primary tumors are marked by the surface protein, CD36—a scavenger receptor that binds fatty acids. The researchers initially identified the cells by examining genes upregulated in non-cycling tumor cells, finding increased expression of genes involved in lipid metabolism, transport, and storage—all processes downstream of CD36.
When the researchers knocked down CD36 with short hairpin RNA before the injecting oral cancer cells into mice, they prevented the cells from seeding metastatic tumors in the lymph nodes of 80 percent to 100 percent of the animals without significantly changing the frequencies of primary tumors. “What’s really cool here is that they showed that CD36 wasn’t necessary for self-renewal, but was necessary for dissemination and metastasis,” said Justin Lathia, a cell and molecular biologist at the Cleveland Clinic who was not involved in the work. This study, he added, demonstrates that metastatic cells don’t have to be cancer stem cells.
It also suggests that metastatic cells may have their own unique metabolic regulation. The IRB team demonstrated that feeding mice a high-fat diet increased the size and number of metastatic lymph node tumors. This effect was lost when CD36 was knocked down. The researchers generated the same effect when they pretreated the cancer cells in culture with a dietary fatty acid called palmitic acid. Lathia note that while this finding could provide insight into the link between obesity and cancer, “human diets are far more complex than what we have here.”

Thursday, January 19, 2017

Effortless Weightloss For Cancer and Diabetes Fermentation Vessels...,

impactjournals |  Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD. Weight reduction was not attributable to decreased HFD intake, enhanced energy expenditure or malabsorption. MTX or CY dosing significantly depleted both adipose tissue and preadipocyte progenitors. Remarkably, however, despite continued high fat feeding, a compensatory increase in hepatocyte lipid storage was not observed, but rather the opposite. Gene microarray liver analyses demonstrated that HFD mice receiving MTX or CY experienced significantly inhibited lipogenesis and lipid storage, whereas Enho (energy homeostasis) gene expression was significantly upregulated. Further metabolic studies employing a human hepatocellular line revealed that MTX treatment preserved robust oxidative phosphorylation, but also promoted mitochondrial uncoupling with a surge in proton leak. This is the first report that certain optimally dosed chemotherapeutic agents can induce weight loss in morbidly obese mice without reduced dietary intake, apparently by depleting stores of adipocytes and their progenitors, curtailment of lipogenesis, and inconspicuous disposal of incoming dietary lipid via a steady state partial uncoupling of mitochondrial oxidative phosphorylation.