Studying Mental Illness by Using Artificial 3D Human “Mini-Brains”

A better understanding of mental illness allows for more effective treatments of it, and this highly complex research looks to be a positive contribution to that.

Article: 3-D human ‘mini-brains’ shed new light on genetic underpinnings of major mental illness

Major mental illnesses such as schizophrenia, severe depression and bipolar disorder share a common genetic link. Studies of specific families with a history of these types of illnesses have revealed that affected family members share a mutation in the gene DISC1. While researchers have been able to study how DISC1 mutations alter the brain during development in animal models, it has been difficult to find the right tools to study changes in humans. However, advancements in engineering human stem cells are now allowing researchers to grow mini-organs in labs, and gene-editing tools can be used to insert specific mutations into these cells.

Researchers from Brigham and Women’s Hospital are leveraging these new technologies to study the effects of DISC1 mutations in cerebral organoids — “mini brains” — cultured from human stem cells. Their results are published in Translational Psychiatry.

“Mini-brains can help us model brain development,” said senior author Tracy Young-Pearse, PhD, head of the Young-Pearse Lab in the Ann Romney Center for Neurologic Diseases at BWH. “Compared to traditional methods that have allowed us to investigate human cells in culture in two-dimensions, these cultures let us investigate the three-dimensional structure and function of the cells as they are developing, giving us more information than we would get with a traditional cell culture.”

The researchers cultured human induced pluripotent stem cells (iPSCs) to create three-dimensional mini-brains for study. Using the gene editing tool CRISPR-Cas9, they disrupted DISC1, modeling the mutation seen in studies of families suffering from these diseases. The team compared mini-brains grown from stem cells with and without this specific mutation.

DISC1-mutant mini-brains showed significant structural disruptions compared to organoids in which DISC1 was intact. Specifically, the fluid-filled spaces, known as ventricles, in the DISC1-mutant mini-brains were more numerous and smaller than in controls, meaning that while the expected cells are present in the DISC1-mutant, they are not in their expected locations. The DISC1-mutant mini-brains also show increased signaling in the WNT pathway, a pathway known to be important for patterning organs and one that is disrupted in bipolar disorder. By adding an inhibitor of the WNT pathway to the growing DISC1-mutant mini-brains, the researchers were able to “rescue” them — instead of having structural differences, they looked similar to the mini-brains developed from normal stem cells. This suggests that the WNT pathway may be responsible for the observed structural disruption in the DISC1-mutants, and could be a potential target pathway for future therapies.

Metallodrug Effective in “Taming” Antibiotic Resistant Superbugs

Metallodrugs are pharmaceuticals that use metal as an active ingredient, and according to the research, this one is able to substantially reduce the dangerous advancement of antibiotic resistance. More hospitals and medical researchers should therefore know about this.

Antimicrobial resistance posed by “superbugs” has been a major public health issue of global concern. Drug-resistant infections kill around 700,000 people worldwide each year. The figure could increase up to ten million by 2050, exceeding the number of deaths caused by cancers, according to figures of the World Health Organization (WHO).

Current clinical options for treating antibiotic resistant infections include increasing the prescribed antibiotic dose or using a combination therapy of two or more antibiotics. This might potentially lead to overuse of antibiotics, producing superbugs more resistant to antibiotics. Nevertheless, the development of antibiotic resistance far outruns the approvals of new antibacterial agents. While it may take a decade and cost an unusual high investment of USD 1 billion in average to bring a new drug to market, generating resistance to a new drug only requires a short couple of years by bacteria. Scientists and clinicians are in desperate need to discover an economic, effective, safe alternative strategy to meet the global public health challenge of antimicrobial resistance.

A research team led by Professor Sun Hongzhe of the Department of Chemistry, Faculty of Science and Dr Richard Kao Yi-Tsun of the Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong (HKU) discovered an alternative strategy by repositioning colloidal bismuth subcitrate (CBS), an antimicrobial drug against Helicobacter pylori (H. pylori) -related ulcer.

They found the bismuth-based metallodrug to effectively paralyze multi-resistant superbugs, e.g. Carbapenem-resistant Enterobacteriaceae (CRE) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) and significantly suppress the development of antibiotic resistance, allowing the lifespan of currently-used antibiotic to be largely extended. CRE and CRKP can cause deadly infections such as bacteremia, pneumonia, and wound infections.

The team is the first globally to link the “resistance-proof” ability of metallo-drug to the treatment of superbugs. This bismuth drug-based therapy looks set to become the last-line strategy against superbugs infections apart from development of new antibiotics. Since CBS is a US Food and Drug Administration (FDA)-approved drug, it will hopefully be rapidly ready for human clinical trials.

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More importantly, the brand-new therapy allows the dose of antibiotics to be reduced by 90% to attain the same level of effectiveness, and the development of NDM-1 resistance to be significantly slowed down, which will largely extend the life cycle of currently used antibiotics.

In the mouse model of NDM-1 bacterial infection, combination therapy comprising CBS and Carbapenem significantly prolonged the life expectancy and raised the eventual survival rate of infected mice by more than 25 percentage points compared to Carbapenem monotherapy. The research team now concentrates on using CBS-based therapy in other animal infection models, e.g. urinary tract infection (UTI), hoping to offer a more extensive approach to combat with antibiotic resistant superbugs.

Dr Ho found the results very encouraging, he said: “There is currently no effective approach to overcome the NDM superbug. Bismuth has been used clinically for decades. Knowing that it can tame the NDM is like “a good rain after a long drought” for the scientific community.”

“Super Sponge” Polymer to Mop Up Oil Spills Created

Something for certain communities to think about using when they inevitably suffer effects of an oil spill, as there are still way too many oil pipelines around the world. It really is stupid for them to still exist at such scale — in the U.S., Keystone XL unfortunately was approved, and in Canada Trudeau keeps campaigning for the oil pipelines, disillusioning a lot of Canadians in the process.

Oil spills could be soaked up by a new floating substance that combines waste from the petroleum industry and cooking oil, according to new research led by South Australia’s Flinders University.

The new polymer, made from sulphur and canola cooking oil, acted like a sponge to remove crude oil and diesel from seawater, according to a new study published in the Advanced Sustainable Systems journal. The polymer can be squeezed to remove the oil and then reused.

The lead researcher, Dr Justin Chalker, said it had the potential to be a cheap and sustainable recovery tool in areas affected by oil spills.

“We anticipate that when we get to economies of scale we will be able to compete in price with other materials that are used to soak up oil,” said Chalker, senior lecturer in synthetic chemistry at Flinders University.

“Our goal is for this to be used globally. It is inexpensive, and we have an eye for it to be used in parts of the world such as the Amazon Basin in Ecuador and the Niger Delta that don’t have access to solutions to oil spills.”

The International Tanker Owners Pollution Federation says about 7,000 tonnes of crude oil were spilt into oceans last year.

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The Flinders University research is just six months ago but Chalker said the new polymer had the potential to be less expensive and more sustainable than current clean-up tools such as polypropylene fibres and polyurethane foam.

Cardi B is Correct About the Importance of Social Security

It’s good that a rapper like Cardi B is into studying politics, since you either turn on to politics or politics turns onto you.

Sen. Bernie Sanders (I-Vt.) embraced a newfound ally this week when he tweeted his agreement with a statement made by rap artist Cardi B about strengthening Social Security.

In a recent GQ interview, Cardi B shared her interest in politics and her admiration for President Franklin D. Roosevelt and his establishment of a social safety net through the New Deal and laws like the Social Security Act of 1935.

“This man was suffering from polio at the time of his presidency, and yet all he was worried about was trying to make America great—make America great again for real. He’s the real ‘Make America Great Again,’ because if it wasn’t for him, old people wouldn’t even get Social Security,” she said.

[…]

Sanders is a long-time advocate of strengthening the system which ensures a financial safety net for senior citizens—and on which Republicans could wage an attack this year, with Sen. Marco Rubio (R-Fla.) claiming in December that the program is a major “driver of our debt,” just before the GOP pushed through a law giving tax cuts to the wealthiest Americans.

The Vermont senator introduced a proposal last year that would require Americans who make more than $250,000 per year to pay the same percentage of their income into the Social Security system as lower-income and middle-class households do, which would increase benefits for low-income seniors.

Artificial Mole as Early Cancer Detection in Development

For those of you who aren’t enthused about some of the other modern methods of cancer screenings, this artificial mole will possibly provide another avenue sometime in the next several years or so.

Alongside cardiovascular disease, cancer has become the top cause of death in industrialised countries. Many of those affected are diagnosed only after the tumour has developed extensively. This often reduces the chance of recovery significantly: the cure rate for prostate cancer is 32 percent and only 11 percent for colon cancer. The ability to detect such tumours reliably and early would not only save lives, but also reduce the need for expensive, stressful treatment.

Researchers working with Martin Fussenegger, Professor at the Department of Biosystems Science and Engineering at ETH Zurich in Basel, have now presented a possible solution for this problem: a synthetic gene network that serves as an early warning system. It recognises the four most common types of cancer — prostate, lung, colon and breast cancer — at a very early stage, namely when the level of calcium in the blood is elevated due to the developing tumour.

The early warning system comprises a genetic network that biotechnologists integrate into human body cells, which in turn are inserted into an implant. This encapsulated gene network is then implanted under the skin where it constantly monitors the blood calcium level.

As soon as the calcium level exceeds a particular threshold value over a longer period of time, a signal cascade is triggered that initiates production of the body’s tanning pigment melanin in the genetically modified cells. The skin then forms a brown mole that is visible to the naked eye.

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The researchers used calcium as the indicator of the development of the four types of cancer, as it is regulated strongly in the body. Bones serve as a buffer that can balance out concentration differences. However, when too much calcium is detected in the blood, this may serve as a sign for one of the four cancers.

“Early detection increases the chance of survival significantly,” says Fussenegger. For example, if breast cancer is detected early, the chance of recovery is 98 percent; however, if the tumour is diagnosed too late, only one in four women has a good chance of recovery. “Nowadays, people generally go to the doctor only when the tumour begins to cause problems. Unfortunately, by that point it is often too late.”

The implant also has an additional advantage: “It is intended primarily for self-monitoring, making it very cost effective,” explains the ETH professor.

[…]

So far, this early warning implant is a prototype; the associated work recently published in the journal Science Translational Medicine is a feasibility study. The researchers have tested their early warning system in a mouse model and on pig skin. It functioned reliably during these tests. Moles developed only when the calcium concentration reached a high level.

[…]

The concept of the “biomedical tattoo,” as Fussenegger describes this new finding, would also be applicable to other gradually developing illnesses, such as neurodegenerative diseases and hormonal disorders. In principle, the researchers could replace the molecular sensor to measure biomarkers other than calcium.

Last Week Tonight Episode on ‘Long and Infuriatingly Proud History’ of Corporate Tax Cheating

It’s a pretty good video (link) based on its evidence and presentation, and I say that as someone who has spent a fair amount of time studying corporate tax systems.

Comedian John Oliver pulled no punches (well, he pulled a few) during Sunday night’s episode of “Last Week Tonight,” especially in the feature segment in which he eviscerated the U.S. tax system by revealing just how endlessly favorable it is to corporations and the wealthy at the expense of everybody else.

Citing last year’s massive tax giveaway to the rich, which will ultimately raise taxes on tens of millions lower-income families, Oliver says, “We just had a huge chance to reform our tax code and we absolutely blew it.”

As The Week details, Oliver goes on to pillory the ability for corporations to avoid taxes by exploiting loopholes and a worldwide web of tax shelters:

Oliver walked through the “long and infuriatingly proud history” of corporate tax avoidance, with a special nod to Apple and Google for being top “innovators in weaselly accounting,” though GE and other huge companies paid zero federal taxes for much of this century. The new tax bill does force some of those companies to pay taxes on money stashed overseas, but at bargain rates — a gamble that did not pay off in terms of job creation in 2004, and probably won’t this time either, Oliver said.

Study: 95% of World Population Exposed to Harmful Air Pollution

It’d thus be a good idea to redesign the energy systems of the world to use clean energy instead of fossil fuels such as oil and coal. Last year a major study found that pollution caused 9 million deaths and lead $4.6 trillion in damages annually.

More than 95 percent of people worldwide are exposed to dangerous air pollution, which kills millions each year and threatens billions more, according to a new analysis.

State of Global Air 2018: A Special Report on Global Exposure to Air Pollution and Its Disease Burden (pdf), published by the Health Effects Institute (HEI), details how exposure to air pollution—both indoor and outdoor—poses a mounting threat to public health.

Researchers found that air pollution is the top environmental cause of death globally, and ranks fourth overall among risk factors —behind high blood pressure, smoking, and dietary choices.

Household air pollution and ambient particular matter—a component of outdoor pollution—were listed individually among the top ten risk factors, and were tied to a combined 6.7 million deaths in 2016, the last year studied. Ozone, a harmful gas that contributes to outdoor pollution, was listed separately and tied to 234,000 deaths from chronic lung disease.

The study, said HEI president Dan Greenbaum, “leads a growing worldwide consensus—among the WHO, World Bank, International Energy Agency and others—that air pollution poses a major global public health challenge.”

“Nowhere is that risk more evident than in the developing world,” Greenbaum noted, “where a third of the world’s population faces a double burden of indoor and outdoor air pollution.”

The report found that “the elderly in low- and middle-income countries experience the greatest loss of healthy life-years due to the non-communicable diseases” linked to air pollution, such as cardiovascular disease, stroke, lung cancer, and COPD.

The new analysis comes as the Trump administration moves to scale back air pollution protections to cater to U.S. manufacturers, part of the administration and Environmental Protection Agency’s broader deregulatory agenda.

Recent studies have shown that similar to the rest of the world, non-White Americans and those living in poverty are more likely to be exposed to polluted air.