Human genome decoded with pocket-sized device

Scientists used a portable device no bigger than a cellphone to sequence the most complete human genome ever assembled with a single technology, according to a study .

The breakthrough, detailed in the journal Nature Biotechnology, brings us closer to the day when family doctors will order up genome scans during a regular check-up along with blood work, the authors suggested.

"We are definitely approaching the point where sequencing genomes will become a routine part of advanced clinical exams," lead author Matthew Loose, a professor at the University of Nottingham, told AFP.

The new sequencing method is the first to read long, unbroken strands of DNA, yielding a final result that is 99.88 percent accurate.

"The process of assembling a genome is like piecing together a jigsaw puzzle," said co-author Nicholas Loman, a scientist at the Institute of Microbiology and Infection and the University of Birmingham.

"The ability to produce extremely long sequencing reads is like finding very large pieces of the puzzle."

Critically, the so-called nanopore technology sheds light on poorly understood regions of the genome governing the body's immune responses and tumour growth.

This may help detect cancer DNA in the blood, and "pick up tumours before they are symptomatic or visible through radiological techniques," said Loman.

In the case of a patient with a suspected infection, the sequencing can be used to ferret out the genome of a virus or bacteria, he told AFP.

"We could also simultaneously look at how the patient is responding to that infection," he added, noting that each individual's immune system is different.

Likewise for sequencing a person's microbiome, the vast community of microbes we each host, mostly in the digestive tract.

Like making a cup of tea

"For personalised medicine, we will want to build up a picture of how individuals may respond to antibiotics and anti-cancer drugs," Loman said.

The human genome is composed of more than three billion pairing of building-block molecules, and grouped into some 25,000 genes.

It contains the codes and instructions that tell the body how to grow and develop. Flaws in the instructions can lead to disease.

The first decoding of a human genome -- completed in 2003 -- was a Manhattan Project-like effort: it took 15 years, cost three billion dollars, and marshalled hundreds of scientists and the computing power from 20 major universities and research institutes.

The new sequencing -- carried out by a dozen researchers and half-a-dozen hand-held devices called MinIONs -- cost a few thousand dollars and took three weeks to complete.

"In five to ten years, genetic sequencing will be a ubiquitous as boiling a kettle or making a cup of tea," predicted co-author Andrew Beggs, a professor at the University of Birmingham, one of nine institutions involved in the project.

The researchers pieced together the genome by passing strands of DNA through minuscule tube-like structures -- manufactured by Oxford Nanopore Technologies -- along with electrically charged atoms.

Changes in the electrical current identify DNA molecules, which can then be mapped.

Complete sequencing is not to be confused with the gene kits offered by companies such as 23andMe and deCODEme, which only provide DNA snapshots, not the whole shebang.

There are only four molecular building blocks of DNA: adenine (A), cytosine (C), guanine (G), and thymine (T).

New gene-editing allow for ultra-precise changes and corrections in DNA coding.

Scientists find new type of ice inside diamonds

A rare form of ice has been found inside diamonds that were newly unearthed around the world, according to a study.

The type of ice, known as ice-VII, features a cubic shape and is about 1.5 times as dense as the regular ice -- ice I.

Different from other solids, whose atoms squeeze together under higher forms of pressure, water-based ice rearrange themselves into new structures when subjected to increasing pressure.

For example, if you press down hard enough on ice-I, it will transform into ice-II, which has a rhombohedral structure. Increase the pressure once gain and the atoms will rearrange themselves into ice-III, then IV, V, VI and VII.

Once it reaches the phase of ice-VII, the structure remains fairly stable even as the pressure increases.

The discovery has cheered the scientists, who previously believed that ice- VII only existed on other planets of the solar systems.

"Water in diamonds is not unknown, but finding this very high pressure form of water ice intact, that was really fortuitous," George Rossman, a mineralogist at Caltech, told the Los Angeles Times. "That's what you call discovery."

Thanks to their discovery, ice-VII has been recognized for the first time as a mineral in the International Mineralogical Assn.

Those diamonds with ice-VII inside were collected from mines in Africa and China.

Scientists transplant memories into snail

Memory transfer has been at the heart of science fiction for decades, but it's becoming more like science fact.

A team successfully transplanted memories by transferring a form of genetic information called RNA from one snail into another.

The snails were trained to develop a defensive reaction.

When the RNA was inserted into snails that had not undergone this process, they behaved just as if they had been sensitised.

The research, published in the journal eNeuro, could provide new clues in the search for the physical basis of memory.

RNA stands for ribonucleic acid; it's a large molecule involved in various essential roles within biological organisms - including the assembly of proteins and the way that genes are expressed more generally.

The scientists gave mild electric shocks to the tails of a species of marine snail called Aplysia californica. After these shocks were administered. the snail's defensive withdrawal reflex - where the snails contract in order to protect themselves from harm.

When the researchers subsequently tapped the snails, they found those that had been given the shocks displayed a defensive contraction lasting about 50 seconds, while those that had not received the shocks contracted for only about one second.

The shocked snails had been "sensitised" to the stimulus.

Purple ink

Scientists extracted RNA from the nervous systems of the snails that received the shocks and injected it into a small number of marine snails that had not been sensitised in this way.

The non-sensitised snails injected with the RNA from the shocked animals behaved as if they had themselves received the tail shocks, displaying a defensive contraction of about 40 seconds.

They saw a similar effect when they did the same thing to sensory nerve cells being studied in petri dishes.

Prof David Glanzman, one of the authors, from the University of California, Los Angeles (UCLA), said the result was "as though we transferred the memory".

He also stressed that the snails did not get hurt: "These are marine snails and when they are alarmed they release a beautiful purple ink to hide themselves from predators. So these snails are alarmed and release ink, but they aren't physically damaged by the shocks," he said.

Traditionally, long-term memories were thought to be stored at the brain's synapses, the junctions between nerve cells. Each neuron has several thousand synapses.

But Prof Glanzman said: "If memories were stored at synapses, there is no way our experiment would have worked."

The UCLA professor of integrative biology holds a different view, believing that memories are stored in the nuclei of neurons. The paper might support hints from studies conducted decades ago that RNA was involved in memory.

The type of RNA relevant to these findings is believed to regulate a variety functions in the cell involved with the development and disease.

The researchers said that the cells and molecular processes in the marine snails are similar to those in humans, despite the fact that the snail has about 20,000 neurons in its central nervous system and humans are thought to have about 100 billion.

The researchers see this result as a step towards alleviating the effects of diseases such as Alzheimer's or post traumatic stress disorder (PTSD).

When asked if this process would be conducive to the transplant of memories laid down through life experiences, Prof Glanzman was uncertain, but he expressed optimism that the greater understanding of memory storage would lead to a greater opportunity to explore different aspects of memory.

Sweeping gene survey reveals new facets of evolution

Who would have suspected that a handheld genetic test used to unmask sushi bars pawning off tilapia for tuna could deliver deep insights into evolution, including how new species emerge?

And who would have thought to trawl through five million of these gene snapshots -- called "DNA barcodes" -- collected from 100,000 animal species by hundreds of researchers around the world and deposited in the US government-run GenBank database?

That would be Mark Stoeckle from The Rockefeller University in New York and David Thaler at the University of Basel in Switzerland, who together published findings last week sure to jostle, if not overturn, more than one settled idea about how evolution unfolds.

It is textbook biology, for example, that species with large, far-flung populations -- think ants, rats, humans -- will become more genetically diverse over time.

But is that true?

"The answer is no," said Stoeckle, lead author of the study, published in the journal Human Evolution.

For the planet's 7.6 billion people, 500 million house sparrows, or 100,000 sandpipers, genetic diversity "is about the same," he told AFP.

The study's most startling result, perhaps, is that nine out of 10 species on Earth today, including humans, came into being 100,000 to 200,000 years ago.

"This conclusion is very surprising, and I fought against it as hard as I could," Thaler told AFP.

That reaction is understandable: How does one explain the fact that 90 percent of animal life, genetically speaking, is roughly the same age?

Was there some catastrophic event 200,000 years ago that nearly wiped the slate clean?

- Simpler, cheaper -

To understand the answer, one has to understand DNA barcoding. Animals have two kinds of DNA.

The one we are most familiar with, nuclear DNA, is passed down in most animals by male and female parents and contains the genetic blueprint for each individual.

The genome -- made up of DNA -- is constructed with four types of molecules arranged in pairs. In humans, there are three billion of these pairs, grouped into about 20,000 genes.

But all animals also have DNA in their mitochondria, which are the tiny structures inside each cell that convert energy from food into a form that cells can use.

Mitochondria contain 37 genes, and one of them, known as COI, is used to do DNA barcoding.

Unlike the genes in nuclear DNA, which can differ greatly from species to species, all animals have the same set of mitochondrial DNA, providing a common basis for comparison.

Mitochondrial DNA is also a lot simpler, and cheaper, to isolate.

Around 2002, Canadian molecular biologist Paul Hebert -- who coined the term "DNA barcode" -- figured out a way to identify species by analysing the COI gene.

"The mitochondrial sequence has proved perfect for this all-animal approach because it has just the right balance of two conflicting properties," said Thaler.

- 'Neutral' mutations -

On the one hand, the COI gene sequence is similar across all animals, making it easy to pick out and compare.

On the other hand, these mitochondrial snippets are different enough to be able to distinguish between each species.

"It coincides almost perfectly with species designations made by specialist experts in each animal domain," Thaler said.

In analysing the barcodes across 100,000 species, the researchers found a telltale sign showing that almost all the animals emerged about the same time as humans.

What they saw was a lack of variation in so-called "neutral" mutations, which are the slight changes in DNA across generations that neither help nor hurt an individual's chances of survival.

In other words, they were irrelevant in terms of the natural and sexual drivers of evolution.

How similar or not these "neutral" mutations are to each other is like tree rings -- they reveal the approximate age of a species.

Which brings us back to our question: why did the overwhelming majority of species in existence today emerge at about the same time?

- Darwin perplexed -

Environmental trauma is one possibility, explained Jesse Ausubel, director of the Program for the Human Environment at The Rockefeller University.

"Viruses, ice ages, successful new competitors, loss of prey -- all these may cause periods when the population of an animal drops sharply," he told AFP, commenting on the study.

"In these periods, it is easier for a genetic innovation to sweep the population and contribute to the emergence of a new species."

But the last true mass extinction event was 65.5 million years ago when a likely asteroid strike wiped out land-bound dinosaurs and half of all species on Earth. This means a population "bottleneck" is only a partial explanation at best.

"The simplest interpretation is that life is always evolving," said Stoeckle.

"It is more likely that -- at all times in evolution -- the animals alive at that point arose relatively recently."

In this view, a species only lasts a certain amount of time before it either evolves into something new or goes extinct.

And yet -- another unexpected finding from the study -- species have very clear genetic boundaries, and there's nothing much in between.

"If individuals are stars, then species are galaxies," said Thaler. "They are compact clusters in the vastness of empty sequence space."

The absence of "in-between" species is something that also perplexed Darwin, he said. 

New material found to eliminate organic pollutants in water

A group of researchers has developed a material capable of the absorption of organic pollutants present in water. According to a study conducted by the University of Seville, two new absorbent materials have shown the capability of eliminating organic pollutants in solution in less than 24 hours.

The appearance of criteria and emerging pollutants in water is a modern theme that has caused the scientific community to research new solutions and alternatives.

Specifically, they have evaluated two types of phyllosilicates: a highly-charged expandable synthetic mica (Na-Mica-4), and one obtained from cation exchange with an organo-functionalised mica (C18-Mica-4). Phyllosilicates are a subclass of silicates and include common mineral in very different environments.

The results show that the material C18-Mica-4 is capable of eliminating the majority of pollutants that were evaluated in urban waste water, as well as surface water and potable water.

The study, also, provided data on the adsorption mechanism and establishes a significant correlation between the physical-chemical properties of the selected criteria and emerging pollutants and the adsorption to the material.

In total, 18 organic pollutants were studied, among which were industrial pollutants, personal care products, and the pharmacologically active ingredients such as anti-inflammatories, antibiotics, anti-epileptics, central nervous system stimulants and lipid-lowering agents, among others.

Within the industrial pollutants, several compounds frequently used as cleaning products were analysed, as well as others used as water- and oil-repellents. With the personal care products, two synthetic preservatives were analysed (methylparaben and propylparaben), both widely used in cosmetic and pharmaceutical products.

Lastly, nine active pharmacological ingredients were also tested (diclofenac, ibuprofen, salicylic acid, trimethoprim, carbamazepine, propranolol, caffeine, clofibric acid and gemfibrozil). Taken to achieve different therapeutic effects, these all end up polluting our waters, essentially, via human excretion. The study was carried out on untreated urban wastewater, treated urban wastewater, surface water from rivers and potable water.

"Studies like this, and others in the same line, are showing the potential of certain adsorbent materials for use in the industrial treatment of water affected by different types of pollution. Obtaining universal materials with a high elimination capacity and which can be used for a wide range of pollutants is the main goal in this area of investigation," said Esteban Alonso, the head of the research project.

The study appears in the journal Environmental Research.

Microplastics may enter foodchain through mosquitoes

Mosquito larvae have been observed ingesting microplastics that can be passed up the food chain, researchers said, potentially uncovering a new way that the polluting particles could damage the environment.

Microplastics — tiny plastic shards broken down from man-made products such as synthetic clothing, car tyres and contact lenses — litter much of the world’s oceans.

Hard to spot and harder to collect, they can seriously harm marine wildlife and are believed to pose a significant risk to human health as they move through the food chain and contaminate water supplies.

Now researchers of the University of Reading believe they have proof for the first time that microplastics can enter our ecosystem by air via mosquitoes and other flying insects.

The team observed mosquito larvae ingesting microscopic plastic beads — similar to the tiny plastic balls found in everyday cosmetic products — before monitoring them through their life cycle.

They found that many of the particles were transferred into the mosquitoes’ adult form, meaning whatever creatures then ate the flying insects in the wild would also ingest the plastic.

“The significance is that this is quite possibly widespread,” Amanda Callaghan, biological scientist at Reading and the lead study author, told AFP.

“We were just looking at mosquitoes as an example but there are lots of insects that live in water and have the same life-cycle with larvae that eat things in water and then emerge as adults.”

The animals known to eat such insects include several species of birds, bats and spiders, all of which are hunted in turn by other animals.

“It’s basically another pathway for pollution that hadn’t been considered previously,” Callaghan said.

Although the team observed the mosquitoes in lab conditions, she said it was “highly possible” the process was already happening in the wild.

Several countries including Britain have banned products containing microbeads, but Callaghan said the scale of the problem was still being discovered.

“It’s a major problem and those plastics already in the environment are going to be with us for a very, very long time,” she said.

Cell-sized robots to help detect diseases

MIT scientists have developed a method to mass produce robots no bigger than a cell that could be used to monitor conditions inside an oil or gas pipeline, or to search out disease while floating through the bloodstream.

The key to making such tiny devices, which the team calls "syncells" (short for synthetic cells), in large quantities lies in controlling the natural fracturing process of atomically-thin, brittle materials.

The process, called "autoperforation," directs the fracture lines so that they produce miniscule pockets of a predictable size and shape.

Embedded inside these pockets are electronic circuits and materials that can collect, record, and output data, according to the study publised in the journal Nature Materials.

The system, developed by researchers at the Massachusetts Institute of Technology in the US, uses a two-dimensional form of carbon called graphene, which forms the outer structure of the tiny syncells.

Ranging in size from that of a human red blood cell, about 10 micrometers across, up to about 10 times that size, these tiny objects "start to look and behave like a living biological cell," said Michael Strano, a professor at MIT.

"In fact, under a microscope, you could probably convince most people that it is a cell," Strano said.

One layer of the material is laid down on a surface, then tiny dots of a polymer material, containing the electronics for the devices, are deposited by a sophisticated laboratory version of an inkjet printer.

Then, a second layer of graphene is laid on top.

"People think of graphene, an ultrathin but extremely strong material, as being 'floppy,' but it is actually brittle," said Strano.

However, rather than considering that brittleness a problem, the team figured out that it could be used to their advantage.

The system controls the fracturing process so that rather than generating random shards of material, like the remains of a broken window, it produces pieces of uniform shape and size.

There are a wide range of potential new applications for such cell-sized robotic devices, said Strano.

As a demonstration, the team "wrote" the letters M, I, and T into a memory array within a syncell, which stores the information as varying levels of electrical conductivity.

This information can then be "read" using an electrical probe, showing that the material can function as a form of electronic memory into which data can be written, read, and erased at will.

It can also retain the data without the need for power, allowing information to be collected at a later time.

The researchers have demonstrated that the particles are stable over a period of months even when floating around in water, which is a harsh solvent for electronics, according to Strano.

New discovery shows glass made from exploding stars

The next time you’re gazing out of the window in search of inspiration, keep in mind the material you’re looking through was forged inside the heart of an exploding ancient star.

An international team of scientists said Friday they had detected silica—the main component of glass—in the remnants of two distant supernovae billions of light years from Earth.

Researchers used NASA’s Spitzer Space Telescope to analyse the light emitted by the collapsing mega-cluster and obtain silica’s “fingerprint” based on the specific wavelength of light the material is known to emit.

A supernova occurs when a large star burns through its own fuel, causing a catastrophic collapse ending in an explosion of galactic proportions. It is in these celestial maelstroms that individual atoms fuse together to form many common elements, including sulphur and calcium.

Silica makes up around 60 percent of the Earth’s crust and one particular form, quartz, is a major ingredient of sand.

As well as glass windows and fibreglass, silica is also an important part of the recipe for industrial concrete.

“We’ve shown for the first time that the silica produced by the supernovae was significant enough to contribute to the dust throughout the Universe, including the dust that ultimately came together to form our home planet,” said Haley Gomez, from Cardiff University’s School of Physics and Astronomy.

“Every time we gaze through a window, walk down the pavement or set foot on a sandy beach, we are interacting with material made by exploding stars that burned millions of years ago.”

In 2016, scientists reported they had found traces of lithium—a metal used in the manufacture of many modern-day electronics—at the heart of exploding nova, a phenomenon that occurs when a white dwarf star absorbs hydrogen from a nearby sun.

The study was published in the Monthly Notices of the Royal Astronomical Society.

Supercomputers help tailor cancer treatments

Attempts to eradicate cancer are often 

 compared to a "moonshot" - the successful effort that sent the first astronauts to the moon.
But imagine if, instead of Newton's second law of motion, which describes the relationship between an object's mass and the amount of force needed to accelerate it, we only had reams of data related to throwing various objects into the air.
This, says Thomas Yankeelov, approximates the current state of cancer research: data-rich, but lacking governing laws and models.
The solution, he believes, is not to mine large quantities of patient data, as some insist, but to mathematize cancer: to uncover the fundamental formulas that represent how cancer, in its many varied forms, behaves.
"We're trying to build models that describe how tumors grow and respond to therapy," said Yankeelov, director of the Center for Computational Oncology at The University of Texas at Austin (UT Austin) and director of Cancer Imaging Research in the LIVESTRONG Cancer Institutes of the Dell Medical School. "The models have parameters in them that are agnostic, and we try to make them very specific by populating them with measurements from individual patients."
The Center for Computational Oncology (part of the broader Institute for Computational Engineering and Sciences, or ICES) is developing complex computer models and analytic tools to predict how cancer will progress in a specific individual, based on their unique biological characteristics.
In December 2017, writing in Computer Methods in Applied Mechanics and Engineering, Yankeelov and collaborators at UT Austin and Technical University of Munich, showed that they can predict how brain tumors (gliomas) will grow and respond to X-ray radiation therapy with much greater accuracy than previous models. They did so by including factors like the mechanical forces acting on the cells and the tumor's cellular heterogeneity. The paper continues research first described in the Journal of The Royal Society Interface in April 2017.
"We're at the phase now where we're trying to recapitulate experimental data so we have confidence that our model is capturing the key factors," he said.
To develop and implement their mathematically complex models, the group uses the advanced computing resources at the Texas Advanced Computing Center (TACC). TACC's supercomputers enable researchers to solve bigger problems than they otherwise could and reach solutions far faster than with a single computer or campus cluster.
According to ICES Director J. Tinsley Oden, mathematical models of the invasion and growth of tumors in living tissue have been "smoldering in the literature for a decade," and in the last few years, significant advances have been made.
"We're making genuine progress to predict the growth and decline of cancer and reactions to various therapies," said Oden, a member of the National Academy of Engineering.
MODEL SELECTION AND TESTING
Over the years, many different mathematical models of tumor growth have been proposed, but determining which is most accurate at predicting cancer progression is a challenge.
In October 2016, writing in Mathematical Models and Methods in Applied Sciences, the team used a study of cancer in rats to test 13 leading tumor growth models to determine which could predict key quantities of interest relevant to survival, and the effects of various therapies.
They applied the principle of Occam's razor, which says that where two explanations for an occurrence exist, the simpler one is usually better. They implemented this principle through the development and application of something they call the "Occam Plausibility Algorithm," which selects the most plausible model for a given dataset and determines if the model is a valid tool for predicting tumor growth and morphology.
The method was able to predict how large the rat tumors would grow within 5 to 10 percent of their final mass.
"We have examples where we can gather data from lab animals or human subjects and make startlingly accurate depictions about the growth of cancer and the reaction to various therapies, like radiation and chemotherapy," Oden said.
The team analyzes patient-specific data from magnetic resonance imaging (MRI), positron emission tomography (PET), x-ray computed tomography (CT), biopsies and other factors, in order to develop their computational model.
Each factor involved in the tumor response - whether it is the speed with which chemotherapeutic drugs reach the tissue or the degree to which cells signal each other to grow - is characterized by a mathematical equation that captures its essence.
"You put mathematical models on a computer and tune them and adapt them and learn more," Oden said. "It is, in a way, an approach that goes back to Aristotle, but it accesses the most modern levels of computing and computational science."
The group tries to model biological behavior at the tissue, cellular and cell signaling levels. Some of their models involve 10 species of tumor cells and include elements like cell connective tissue, nutrients and factors related to the development of new blood vessels. They have to solve partial differential equations for each of these elements and then intelligently couple them to all the other equations.
"This is one of the most complicated projects in computational science. But you can do anything with a supercomputer," Oden said. "There's a cascading list of models at different scales that talk to each other. Ultimately, we're going to need to learn to calibrate each and compute their interactions with each other."
FROM COMPUTER TO CLINIC
The research team at UT Austin - which comprises 30 faculty, students, and postdocs - doesn't only develop mathematical and computer models. Some researchers work with cell samples in vitro; some do pre-clinical work in mice and rats. And recently, the group has begun a clinical study to predict, after one treatment, how an individual's cancer will progress, and use that prediction to plan the future course of treatment.
At Vanderbilt University, Yankeelov's previous institution, his group was able to predict with 87 percent accuracy whether a breast cancer patient would respond positively to treatment after just one cycle of therapy. They are trying to reproduce those results in a community setting and extend their models by adding new factors that describe how the tumor evolves.
The combination of mathematical modeling and high-performance computing may be the only way to overcome the complexity of cancer, which is not one disease but more than a hundred, each with numerous sub-types.
"There are not enough resources or patients to sort this problem out because there are too many variables. It would take until the end of time," Yankeelov said. "But if you have a model that can recapitulate how tumors grow and respond to therapy, then it becomes a classic engineering optimization problem. 'I have this much drug and this much time. What's the best way to give it to minimize the number of tumor cells for the longest amount of time?'"
Computing at TACC has helped Yankeelov accelerate his research. "We can solve problems in a few minutes that would take us 3 weeks to do using the resources at our old institution," he said. "It's phenomenal."
According to Oden and Yankeelov, there are very few research groups trying to sync clinical and experimental work with computational modeling and state-of-the-art resources like the UT Austin group.
"There's a new horizon here, a more challenging future ahead where you go back to basic science and make concrete predictions about health and well-being from first principles," Oden said.
Said Yankeelov: "The idea of taking each patient as an individual to populate these models to make a specific prediction for them and someday be able to take their model and then try on a computer a whole bunch of therapies on them to optimize their individual therapy - that's the ultimate goal and I don't know how you can do that without mathematizing the problem."