Offer gene test to stroke patients, NHS told

A DNA test can show who would benefit from a drug to prevent future brain-clot damage, new guidelines say.

Share Button

Perfection: The Enemy of Evolution

Scientists are often trained to seek out the absolute best solution to a given problem. On a chalk board, this might look something like drawing a graph to find a function’s minimum or maximum point. When designing a turbojet engine, it might mean tweaking the rotor blades’ angles a tiny degree to achieve a tenth of a percent increase in efficiency.

Adrian Bejan, the J.A. Jones Distinguished Professor of Mechanical Engineering at Duke University, was busy demonstrating the former for a class full of students when a thought struck him: this is not how nature operates. Evolution is a sequence of design changes happening on their own in a discernible direction; it never weds itself to a single point on a drawing board. An evolving system or animal is free to simply go with what works. Not so much that its performance suffers greatly, but enough that it opens access to other options near the so-called optimal design.

With science often looking to nature for clues to solve challenges, Bejan wondered if he might look the opposite way, to predict nature before looking at it. If problem solvers and builders were free to miss the absolute highest mark, how much greater might be the range of designs they consider plausible?

That’s the question that Bejan posits in a new paper published online May 16 in the journal Biosystems. Using two relatively simple examples — walkways ferrying passengers off a train and a bird flapping its wings — he discovers that the answer is, “quite a lot.”

“In engineering, design, theater, architecture or even the organization of this university, any form of design benefits from the ability to make good but imperfect decisions and the freedom to move on and contemplate other opportunities for improvement,” Bejan said. “If one is wedded to the idea of the absolute best, nothing new will ever be created.”

In the paper, Bejan first looks at the example of passengers arriving by train and walking across a room with many exit points. With the total area of the room remaining constant but the length and width of the room free to change, he solves for the optimal shape of the room to get all passengers where they’re going the quickest. With the solution equations in hand, he shows that providing even 1% wiggle room for imperfection away from the best performance opens the design space by 28%.

In his second example, Bejan looks at the flapping motion of birds at nearly constant altitude and speed. Considering the various forces involved — drag during gliding, lift created by wing size, speed and body size, among others — he formulates an equation for the rhythm of wings needed to maintain constant speed with minimum effort. While an optimal answer does exist, Bejan once again shows that allowing for just 1% imperfection above the theoretical minimum effort opens the design space by 20%.

Bejan says that he chose these examples because they involved changing only a single variable, a single degree of freedom — the shape for a room or the flapping rhythm for a wing. In more complex examples that involve many variables, these tiny tolerances for imperfection create an even wider range of “good enough” solutions.

The lesson learned is that science now has a predictive idea of how nature works. By focusing less on finding absolute optimal designs, researchers may use the freedom to iteratively move toward entirely new design concepts that wouldn’t otherwise have been within their sight. It also gives designs, methods and entire fields of study the ability to adapt to a changing world.

“The doctrine of chasing the best design is not helpful,” Bejan said. “The teaching of science should go hand-in-hand with the freedom to take a shot, hit the vicinity of the mark and move on. The end goal isn’t just to hit a bullseye, but to keep more arrows in your quiver to keep taking shots over a long period of time.”

This work was supported by a grant from CaptiveAire Systems.

Share Button

Vaping: Tighter rules calls after doubling in children using vapes

A father from north Wales has set up a petition with 100,000 signatures calling for action.

Share Button

Fossil of mosasaur with bizarre ‘screwdriver teeth’ found in Morocco

Scientists have discovered a new species of mosasaur, a sea-dwelling lizard from the age of the dinosaurs, with strange, ridged teeth unlike those of any known reptile. Along with other recent finds from Africa, it suggests that mosasaurs and other marine reptiles were evolving rapidly up until 66 million years ago, when they were wiped out by an asteroid along with the dinosaurs and around 90% of all species on Earth.

The new species, Stelladens mysteriosus, comes from the Late Cretaceous of Morocco and was around twice the size of a dolphin.

It had a unique tooth arrangement with blade-like ridges running down the teeth, arranged in a star-shaped pattern, reminiscent of a cross-head screwdriver.

Most mosasaurs had two bladelike, serrated ridges on the front and back of the tooth to help cut prey, however Stelladens had anywhere from four to six of these blades running down the tooth.

“It’s a surprise,” said Dr Nick Longrich from the Milner Centre for Evolution at the University of Bath, who led the study. “It’s not like any mosasaur, or any reptile, even any vertebrate we’ve seen before.”

Dr Nathalie Bardet, a marine reptile specialist from the Museum of Natural History in Paris, said: “I’ve worked on the mosasaurs of Morocco for more than 20 years, and I’d never seen anything like this before — I was both perplexed and amazed!”

That several teeth were found with the same shape suggests their strange shape was not the result of a pathology or a mutation.

The unique teeth suggest a specialised feeding strategy, or a specialised diet, but it remains unclear just what Stelladens ate.

Dr Longrich said: “We have no idea what this animal was eating, because we don’t know of anything similar either alive today, or from the fossil record.

“It’s possible it found a unique way to feed, or maybe it was filling an ecological niche that simply doesn’t exist today. The teeth look like the tip of a Phillips-head screwdriver, or maybe a hex wrench.

“So what’s it eating? Phillips head screws? IKEA furniture? Who knows.”

The teeth were small, but stout and with wear on the tips, which seemed to rule out soft-bodied prey. The teeth weren’t strong enough to crush heavily armoured animals like clams or sea urchins, however.

“That might seem to suggest it’s eating something small, and lightly armoured — thin-shelled ammonites, crustaceans, or bony fish — but it’s hard to know,” said Longrich. “There were weird animals living in the Cretaceous- ammonites, belemnites, baculites — that no longer exist. It’s possible this mosasaur ate something, and occupied a niche, that simply doesn’t exist anymore, and that might explain why nothing like this is ever seen again.

“Evolution isn’t always predictable. Sometimes it goes off in a unique direction, and something evolves that’s never been seen before, and then it never evolves again.”

The mosasaurs lived alongside dinosaurs but weren’t dinosaurs. Instead, they were giant lizards, relatives of Komodo dragons, snakes, and iguanas, adapted for a life at sea.

Mosasaurs evolved around 100 million years ago, and diversified up to 66 million years ago, when a giant asteroid hit the Yucatan Peninsula in Mexico, plunging the world into darkness.

Although scientists have debated the role of environmental changes towards the end of the Cretaceous in the extinction, Stelladens, along with recent discoveries from of Morocco, suggests that mosasaurs were evolving rapidly up to the very end — they went out at their peak, rather than fading away.

The new study shows that even after years of work in the Cretaceous of Morocco, new species are continuing to be discovered. The reason may be that most species are rare.

The authors of the study predict that in a very diverse ecosystem, it may take decades to find all of the rare species.

“We’re not even close to finding everything in these beds,” said Longrich, “This is the third new species to appear, just this year. The amount of diversity at the end of the Cretaceous is just staggering.”

Nour-Eddine Jalil, a professor at the Natural History Museum and a researcher at Univers Cadi Ayyad in Morocco, said: “The fauna has produced an incredible number of surprises — mosasaurs with teeth arranged like a saw, a turtle with a snout in the form of snorkel, a multitude of vertebrates of various shapes and sizes, and now a mosasaur with star-shaped teeth.

“We would say the works of an artist with an overflowing imagination.

“Morocco’s sites offer an unparalleled picture of the amazing biodiversity just before the great crisis of the end of the Cretaceous.”

Share Button

Novel 3D printing method a ‘game changer’ for discovery, manufacturing of new materials

The time-honored Edisonian trial-and-error process of discovery is slow and labor-intensive. This hampers the development of urgently needed new technologies for clean energy and environmental sustainability, as well as for electronics and biomedical devices.

“It usually takes 10 to 20 years to discover a new material,” said Yanliang Zhang, associate professor of aerospace and mechanical engineering at the University of Notre Dame.

“I thought if we could shorten that time to less than a year — or even a few months — it would be a game changer for the discovery and manufacturing of new materials.”

Now Zhang has done just that, creating a novel 3D printing method that produces materials in ways that conventional manufacturing can’t match. The new process mixes multiple aerosolized nanomaterial inks in a single printing nozzle, varying the ink mixing ratio on the fly during the printing process. This method — called high-throughput combinatorial printing (HTCP) — controls both the printed materials’ 3D architectures and local compositions and produces materials with gradient compositions and properties at microscale spatial resolution.

His research was just published in Nature.

The aerosol-based HTCP is extremely versatile and applicable to a broad range of metals, semiconductors and dielectrics, as well as polymers and biomaterials. It generates combinational materials that function as “libraries,” each containing thousands of unique compositions.

Combining combinational materials printing and high-throughput characterization can significantly accelerate materials discovery, Zhang said. His team has already used this approach to identify a semiconductor material with superior thermoelectric properties, a promising discovery for energy harvesting and cooling applications.

In addition to speeding up discovery, HTCP produces functionally graded materials that gradually transition from stiff to soft. This makes them particularly useful in biomedical applications that need to bridge between soft body tissues and stiff wearable and implantable devices.

In the next phase of research, Zhang and the students in his Advanced Manufacturing and Energy Lab plan to apply machine learning and artificial intelligence-guided strategies to the data-rich nature of HTCP in order to accelerate the discovery and development of a broad range of materials.

“In the future, I hope to develop an autonomous and self-driving process for materials discovery and device manufacturing, so students in the lab can be free to focus on high-level thinking,” Zhang said.

Share Button

Cancer cells use a new fuel in absence of sugar

Researchers at the University of Michigan Rogel Cancer Center have discovered a new nutrient source that pancreatic cancer cells use to grow. The molecule, uridine, offers insight into both biochemical processes and possible therapeutic pathways.

The findings, published in Nature, show that cancer cells can adapt when they don’t have access to glucose. Researchers have previously identified other nutrients that serve as fuel sources for pancreatic cancer; this study adds uridine to the catalog.

Pancreatic tumors have few functioning blood vessels and can’t easily access nutrients that come from the bloodstream, like glucose. Costas Lyssiotis, Ph.D., Maisel Research Professor of Oncology and lead investigator of the study, explained that without the right nutrients, the cancer cells get hungry. “We know they still grow, obviously, but what are they using to grow?” he said. “These findings show that, under certain circumstances, uridine is one of those fuels.”

Asked about impact, Zeribe Nwosu, Ph.D., one of the co-first authors in the study, says “the ability of cancer to switch to alternative nutrients has fascinated me for a long time. Blocking such compensatory switches could lead us to new treatments and that’s the door we hope this study will open.”

Uridine is present in the tumor microenvironment, but its exact source, and how cancer cells access it, remains a mystery. “Part of the picture is it’s in the bloodstream, but we don’t know where it’s coming from specifically,” said Lyssiotis. “Likely, it’s coming from multiple places, and so far we haven’t been able to pin it to a single source.”

Events that Lyssiotis refers to as “times of crisis” — when cells don’t have enough nutrients, because of limited blood access and/or intense competition between cells — could be a clue as to why, and where, cells turn to uridine. “The cancer cells seem to be sensing the concentrations of glucose and uridine in the local environment to inform their adaptation,” says Matt Ward, another co-first author. Lyssiotis’ team recognize this unknown regulatory process, as well as a cancer-promoting mutation in the KRAS gene, which is common in pancreatic cancer, as two ways that cancer cells control their usage of uridine.

Lyssiotis and his team have been working on this research for nearly a decade alongside their collaborators in the Sadanandam lab at the Institute for Cancer Research in London. They used a technology that screens hundreds of different nutrients to see which ones support pancreatic cancer growth. Typically, researchers look at standard nutrients like sugar, protein and fat, but Lyssiotis’s team took an unbiased approach. “We used a large panel with over 20 pancreatic cell lines and around 200 different nutrients to assess different ways pancreatic cancer cells grow,” he explained. “What do they actually metabolize? This method led us to discover uridine.”

This method offers therapeutic insight, too. The findings showed that uridine is metabolized by the enzyme uridine phoshorylase-1, or UPP1. Blocking UPP1 had a major impact on the growth of pancreatic tumors in mice, findings that suggest the importance of testing drugs that block uridine as possible new treatment options.

“There’s potential to better understand and treat pancreatic cancer with new drug targets and new therapeutic approaches,” said Sadanandam, co-author on the study.

More research is needed to determine the best way to move this discovery to the clinic.

Share Button

An electric vehicle battery for all seasons

Many owners of electric vehicles worry about how effective their battery will be in very cold weather. Now a new battery chemistry may have solved that problem.

In current lithium-ion batteries, the main problem lies in the liquid electrolyte. This key battery component transfers charge-carrying particles called ions between the battery’s two electrodes, causing the battery to charge and discharge. But the liquid begins to freeze at sub-zero temperatures. This condition severely limits the effectiveness of charging electric vehicles in cold regions and seasons.

To address that problem, a team of scientists from the U.S. Department of Energy’s (DOE) Argonne and Lawrence Berkeley national laboratories developed a fluorine-containing electrolyte that performs well even in sub-zero temperatures.

“Our team not only found an antifreeze electrolyte whose charging performance does not decline at minus 4 degrees Fahrenheit, but we also discovered, at the atomic level, what makes it so effective,” said Zhengcheng “John” Zhang, a senior chemist and group leader in Argonne’s Chemical Sciences and Engineering division.

This low-temperature electrolyte shows promise of working for batteries in electric vehicles, as well as in energy storage for electric grids and consumer electronics like computers and phones.

In today’s lithium-ion batteries, the electrolyte is a mixture of a widely available salt (lithium hexafluorophosphate) and carbonate solvents such as ethylene carbonate. The solvents dissolve the salt to form a liquid.

When a battery is charged, the liquid electrolyte shuttles lithium ions from the cathode (a lithium-containing oxide) to the anode (graphite). These ions migrate out of the cathode, then pass through the electrolyte on the way into the anode. While being transported through the electrolyte, they sit at the center of clusters of four or five solvent molecules.

During the initial few charges, these clusters strike the anode surface and form a protective layer called the solid-electrolyte interphase. Once formed, this layer acts like a filter. It allows only the lithium ions to pass through the layer while blocking the solvent molecules. In this way, the anode is able to store lithium atoms in the structure of the graphite on charge. Upon discharge, electrochemical reactions release electrons from the lithium that generate electricity that can power vehicles.

The problem is that in cold temperatures, the electrolyte with carbonate solvents begins to freeze. As a result, it loses the ability to transport lithium ions into the anode on charge. This is because the lithium ions are so tightly bound within the solvent clusters. Hence, these ions require much higher energy to evacuate their clusters and penetrate the interface layer than at room temperature. For that reason, scientists have been searching for a better solvent.

The team investigated several fluorine-containing solvents. They were able to identify the composition that had the lowest energy barrier for releasing lithium ions from the clusters at sub-zero temperature. They also determined at the atomic scale why that particular composition worked so well. It depended on the position of the fluorine atoms within each solvent molecule and their number.

In testing with laboratory cells, the team’s fluorinated electrolyte retained stable energy storage capacity for 400 charge-discharge cycles at minus 4 F. Even at that sub-zero temperature, the capacity was equivalent to that of a cell with a conventional carbonate-based electrolyte at room temperature.

“Our research thus demonstrated how to tailor the atomic structure of electrolyte solvents to design new electrolytes for sub-zero temperatures,” Zhang said.

The antifreeze electrolyte has a bonus property. It is much safer than the carbonate-based electrolytes that are currently used, since it will not catch fire.

“We are patenting our low-temperature and safer electrolyte and are now searching for an industrial partner to adapt it to one of their designs for lithium-ion batteries,” Zhang said.

This research appears in Advanced Energy Materials. In addition to John Zhang, Argonne authors are Dong-Joo Yoo, Qian Liu and Minkyu Kim. Berkeley Lab authors are Orion Cohen and Kristin Persson.

This work was funded by the DOE Office of Energy Efficiency and Renewable Energy, Vehicle Technologies Office.

Share Button

10 pesticides toxic to neurons involved in Parkinson’s

Researchers at UCLA Health and Harvard have identified 10 pesticides that significantly damaged neurons implicated in the development of Parkinson’s disease, providing new clues about environmental toxins’ role in the disease.

While environmental factors such as pesticide exposure have long been linked to Parkinson’s, it has been harder to pinpoint which pesticides may raise risk for the neurodegenerative disorder. Just in California, the nation’s largest agricultural producer and exporter, there are nearly 14,000 pesticide products with over 1,000 active ingredients registered for use.

Through a novel pairing of epidemiology and toxicity screening that leveraged California’s extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons. The neurons play a key role in voluntary movement, and the death of these neurons is a hallmark of Parkinson’s.

Further, the researchers found that co-exposure of pesticides that are typically used in combinations in cotton farming were more toxic than any single pesticide in that group.

For this study, published May 16 in Nature Communications, UCLA researchers examined exposure history going back decades for 288 pesticides among Central Valley patients with Parkinson’s disease who had participated in previous studies. The researchers were able to determine long-term exposure for each person and then, using what they labeled a pesticide-wide association analysis, tested each pesticide individually for association with Parkinson’s. From this untargeted screen, researchers identified 53 pesticides that appeared to be implicated in Parkinson’s — most of which had not been previously studied for a potential link and are still in use.

Those results were shared for lab analysis led by Richard Krolewski, MD, PhD, an instructor of neurology at Harvard and neurologist at Brigham and Women’s Hospital. He tested the toxicity for most of those pesticides in dopaminergic neurons that had been derived from Parkinson’s patients through what’s known as induced pluripotent stem cells, which are a type of “blank slate” cell that can be reprogrammed into neurons that closely resemble those lost in Parkinson’s disease.

The 10 pesticides identified as directly toxic to these neurons included: four insecticides (dicofol, endosulfan, naled, propargite), three herbicides (diquat, endothall, trifluralin), and three fungicides (copper sulfate [basic and pentahydrate] and folpet). Most of the pesticides are still in use today in the United States.

Aside from their toxicity in dopaminergic neurons, there is little that unifies these pesticides. They have a range of use types, are structurally distinct, and do not share a prior toxicity classification.

Researchers also tested the toxicity of multiple pesticides that are commonly applied in cotton fields around the same time, according to California’s pesticide database. Combinations involving trifluralin, one of the most commonly used herbicides in California, produced the most toxicity. Previous research in the Agricultural Health Study, a large research project involving pesticide applicators,had also implicated trifluralin in Parkinson’s.

Kimberly Paul, PhD, a lead author and assistant professor of neurology at UCLA, said the study demonstrated their approach could broadly screen for pesticides implicated in Parkinson’s and better understand the strength of these associations.

“We were able to implicate individual agents more than any other study has before, and it was done in a completely agnostic manner,” Paul said. “When you bring together this type of agnostic screening with a field-to-bench paradigm, you can pinpoint pesticides that look like they’re quite important in the disease.”

The researchers are next planning to study epigenetic and metabolomic features related to exposure using integrative omics to help describe which biologic pathways are disrupted among Parkinson’s patients who experienced pesticide exposure. More detailed mechanistic studies of the specific neuronal processes impacted by pesticides such as trifluralin and copper are also underway at the Harvard/Brigham and Women’s labs. The lab work is focused on distinct effects on dopamine neurons and cortical neurons, which are important for the movement and cognitive symptoms in Parkinson’s patients, respectively. The basic science is also expanding to studies of pesticides on non-neuronal cells in the brain — the glia — to better understand how pesticides influence the function of these critical cells.

Other authors include Edinson Lucumi Moreno, Jack Blank, Kristina M. Holton, Tim Ahfeldt, Melissa Furlong, Yu Yu, Myles Cockburn, Laura K. Thompson, Alexander Kreymerman, Elisabeth M. Ricci-Blair, Yu Jun Li, Heer B. Patel, Richard T Lee, Jeff Bronstein, Lee L. Rubin, Vikram Khurana, and Beate Ritz.

Share Button

One step closer to developing a potentially ultraprotective sunscreen from our own melanin

A new discovery about the structure of melanin has brought scientists one step closer to developing a new, potentially ultra-protective sunscreen derived from a biological substance found in nearly all organisms. Researchers from McGill’s Department of Chemistry, in collaboration with The Ohio State University and the University of Girona, have announced a major advance in understanding the fundamental structure of melanin and one of its components that turns light into heat, protecting the body from sun damage.

Melanin, the pigment that gives humans their skin, eye, and hair colour, is the body’s first and best natural defense against the sun’s harmful rays. Cosmetics companies have long tried to harness the protective powers of natural and synthetic melanin for use in chemical sunscreens and other personal care products. For example, melanin could, in theory, be used to produce a radiation barrier that augments skin care products by matching a more diverse range of natural skin tones. But melanin is so notoriously unstable and difficult to study that, thus far, scientists have not been able to see what it looks like at the molecular level, resulting in a slow, trial-and-error approach to its potential use in personal care products.

“As we gain a better understanding of the structure of melanin, we should be able to predictably make alternatives that perform better than what is currently available,” said Jean-Philip Lumb, one of the lead authors of the paper. The study found that the melanin component converted light into heat from all wavelengths, spanning the ultraviolet to the infrared, offering a broad spectrum of protection. The molecule was also remarkably small, which the researchers say has practical benefits because the number of atoms needed to provide this level of sun protection is fewer than anything reported up to now. “We’ve taken a major step forward in understanding a new mechanism for how melanin can serve as a sunscreen,” Lumb said.

Share Button

Lucy Letby trial: Nurse accuses doctors of conspiracy against her

Lucy Letby accuses a “gang of four” of “apportioning blame” on to her “to cover up” hospital failings.

Share Button