In a study by Fan et al., healthy adults performed two tasks while the researchers recorded brain activity using functional magnetic resonance imaging: they identified pieces of furniture in pictures and produced drawings of those pieces of furniture. The researchers used machine learning to discover similar patterns of brain activity across both tasks within the occipital cortex, an area of the brain important for visual processing. This means people recruit the same neural representation of an object whether they are drawing it or seeing it.

As the participants drew each object multiple times, the activity patterns in occipital cortex remained unchanged, but the connection between occipital cortex and parietal cortex, an area involved in motor planning, grew more distinct. This suggests that drawing practice enhances how the brain shares information about an object between different regions over time.

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By chemically tweaking the ends of the DNA to be inserted, the new technique is up to five times more efficient than current approaches. The researchers saw improvements at various genetic locations tested in a human kidney cell line, even seeing 65% insertion at one site where the previous high had been 15%.

Led by chemical and biomolecular engineering professor Huimin Zhao, the researchers published their work in the journal Nature Chemical Biology.

Researchers have found CRISPR to be an efficient tool to turn off, or “knock out,” a gene. However, in human cells, it has not been a very efficient way to insert or “knock in” a gene.

“A good knock-in method is important for both gene-therapy applications and for basic biological research to study gene function,” said Zhao, who leads the biosystems design theme at the Carl R. Woese Institute for Genomic Biology at Illinois. “With a knock-in method, we can add a label to any gene, study its function and see how gene expression is affected by cancer or changes in chromosome structure. Or for gene-therapy applications, if someone has a disease caused by a missing gene, we want to be able to insert it.”

Searching for a way to increase efficiency, Zhao’s group looked at 13 different ways to modify the inserted DNA. They found that small changes to the very end of the DNA increased both the speed and efficiency of insertion.

Then, the researchers tested inserting end-modified DNA fragments of varying sizes at multiple points in the genome, using CRISPR-Cas9 to precisely target specific sites for insertion. They found efficiency improved two to five times, even when inserting larger DNA fragments — the most difficult insertion to make.

“We speculate that the efficiency improved so much because the chemical modification to the end stabilizes the DNA we are inserting,” Zhao said. “Normally, when you try to transfer DNA into the cell, it gets degraded by enzymes that eat away at it from the ends. We think our chemical addition protects the ends. More DNA is getting into the nucleus, and that DNA is more stable, so that’s why I think it has a higher chance to be integrated into the chromosome.”

Zhao’s group already is using the method to tag essential genes in gene function studies. They purposely used off-the-shelf chemicals to modify the DNA fragments so that other research teams could use the same method for their own genetic studies.

“We’ve developed quite a few knock-in methods in the past, but we never thought about just using chemicals to increase the stability of the DNA we want to insert,” Zhao said. “It’s a simple strategy, but it works.”

The spin states of the new compounds are stable for at least several days. “This is achieved by a design trick that resembles the fundamental electronic circuits in computers, the so-called flip-flops. Bistability or switching between 0 and 1 is realized by looping the output signal back to the input,” says experimental physicist Dr. Manuel Gruber from Kiel University. The new molecules have three properties that are coupled with each other in such a feedback loop: their shape (planar or flat), the proximity of two subunits, called coordination (yes or no), and the spin state (high-spin or low-spin). Thus, the molecules are locked either in one or the other state. Upon sublimation and deposition on a silver surface, the switches self-assemble into highly ordered arrays. Each molecule in such an array can be separately addressed with a scanning tunneling microscope and switched between the states by applying a positive or negative voltage.

“Our new spin switch realizes in just one molecule what takes several components like transistors and resistors in conventional electronics. That’s a big step towards further miniaturisation,” Dr. Manuel Gruber und organic chemist Prof. Dr. Rainer Herges explain. The next step will be to increase the complexity of the compounds to implement more sophisticated operations.

Molecules are the smallest constructions that can be designed and built with atomic precision and predictable properties. Their response to electrical or optical stimuli and their custom-designed chemical and physical functionality make them unique candidates to develop new classes of devices such as controllable surface catalysts or optical devices.

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Journal Reference:

1. Alexander Köbke, Florian Gutzeit, Fynn Röhricht, Alexander Schlimm, Jan Grunwald, Felix Tuczek, Michał Studniarek, Danilo Longo, Fadi Choueikani, Edwige Otero, Philippe Ohresser, Sebastian Rohlf, Sven Johannsen, Florian Diekmann, Kai Rossnagel, Alexander Weismann, Torben Jasper-Toennies, Christian Näther, Rainer Herges, Richard Berndt, Manuel Gruber. Reversible coordination-induced spin-state switching in complexes on metal surfaces. Nature Nanotechnology, 2019; DOI: 10.1038/s41565-019-0594-8

Researchers at the Center for Soft and Living Matter, within the Institute for Basic Science (IBS, South Korea) found that the temperature increase caused by the probe beam could be utilized to generate a signal per se for detecting objects. Notably, this so-called “active thermal detection” enables super-resolution imaging at all scales, compared to conventional techniques whose application are confined to microcopy only. Super-resolution unveils the small details of an image, making it possible to resolve previously hidden figures. Francois Amblard, the second author of the study says, “Nobody tried to use thermal radiation for super-resolution, even though this signal is so noticeable that it cannot be missed. Our first and deceptively simple idea is to detect objects with their obvious signal, the thermal radiation.”

When an object is illuminated by a probe beam with enough energy to cause its temperature to jump, its thermal radiation soars. In fact, we can find the application of such temperature increase in our everyday life, e.g. for screening feverish passengers at airport controls. When an object undergoes a temperature increase, it emits an intense thermal radiation. The researchers theoretically verified the super-linearity of thermal radiation. They gave an exact quantification of the number of photons emitted by a heated object and showed that even a small temperature increase resulted in a huge change in the emission of light. This process, together with active heating and a detection scheme, could help detecting objects at a very high resolution.

Moreover, the super-resolution factor can be arbitrarily cranked up if a sufficiently high temperature is reached. “Our theory predicts that the emission spatial profile can be made arbitrarily narrow, leading to an improved localization of objects, and even in principle to an arbitrarily large super-resolution. One expects then to be able to better resolve two nearby targets, or to better detect the shape of a target,” explains, Guillaume Graciani, the first author of the study.

Super resolution techniques allowed us to see what was previously unseen, but its magic has been working only in microscopy so far. Notably, this study presents the thermal radiation and its intrinsic super-linearity as a universal way to super resolve objects at all scales from microscopic imaging to flying objects such as planes. The active thermal detection also finds applications in thermal imaging for non-destructive testing, Lidar and Radar technologies for self-driving cars, mid- or long-range detection of stealth objects. It also opens a new field of applications for the most recent thermal photodetectors, such as superconducting nanowire single-photon detectors or HgCdTe avalanche photodiodes. Finally, new kind of thermal probes could be designed for super-resolved thermal detection or imaging at microscopic scales.

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Led by UdeM cell biologist Jean-François Côté, the team threw 56 “baits” into human cells they were incubating in their laboratory, catching more than 9,000 proteins in the process. The results are published today in the journal Nature Cell Biology.

The goal was to identify the proteins that attach to those of the Rho family, famous in the cell biology world since the discovery in the early 1990s that they dictate how pieces of the cell skeleton — the “cytoskeleton” — are assembled.

In humans, the 20 members of the Rho family are scattered on the inner surface of cell membranes and act like small switches. When a signal from outside or inside the cell activates them, they stimulate other proteins to force the cytoskeleton to add or remove parts to its framework.

Out of all these proteins, only three, to date, have been thoroughly studied by researchers: Cdc42, Rac1 and RhoA. Cdc42 acts as the lead protein: it indicates the path that white blood cells must take to find a site of infection. Rac1 activates the engines that drive a non-muscular cell forward. RhoA stimulates the formation of fibres that allow cells to contract or form resistant tissues as they come together to produce, for example, the wall of a blood vessel.

But what are the other proteins doing? And what other proteins do they interact with? To find out, Coté and his team went fishing for answers.

Two-headed proteins

Into human cells growing in incubators in their lab, they cast their baited lines, forcing these cells to produce proteins with two heads, one containing a single side of a protein in the Rho family, the other a “biotin ligase” enzyme. The latter acts like an elite sniper in the cell, luring and labelling every passing protein with the help of its partner, a member of the Rho family. Every protein that approached the bait was thus labeled with biotin. Next, Côté and his team had to shred the cells to identify, one by one, each labelled protein.

Using 28 two-headed proteins and presenting the GTPases — a superfamily of enzymes that function as ‘molecular switches’ and are involved in regulating many cellular processes — in both active and inactive configurations, the team caught a total of 9,939 proteins. Some were already known to the scientists, including the GTPases’ activators and deactivators. But the researchers also discovered hundreds of individual proteins with yet-to-be-defined roles.

These discoveries include the missing link of the cytoskelton Rho process identified in the early ’90s. Back then, researchers noticed that the RhoA protein indirectly activates another protein, ERM, causing it to stabilize the cytoskeleton. But they didn’t know the precise mechanism behind this process. On their “fishing expedition,” Côté and his team found the answer: what forges the link between RhoA and ERM is a protein called SLK.

In their study, the IRCM team also looked at other proteins that, until now, were virtually unknown to biologists, namely GARRE and PLEKHG3. The scientists demonstrated that these proteins naturally attach to the active forms of Rac1 and RhoG, respectively. What’s left to understand is the exact function of these associations. To accelerate the process, the team revealed characteristics of other molecules they caught in their experiments — enough to give raw material to dozens of laboratories worldwide.

Through their research, Côté and his team have not only cleared up a whole area of cell biology, but have also demonstrated the effectiveness of their unique “fishing” method. Côté now plans to use it to better understand how other molecular switches work, especially those in the Ras family, proteins that lie at the centre of many types of cancer.

Writing in the current issue of Nature Climate Change, Toni Lyn Morelli at the U.S. Geological Survey’s Northeast Climate Adaptation Science Center at University of Massachusetts Amherst and her international team of co-authors point out that species across the globe now face concurrent pressures on many fronts. These include habitat degradation and fragmentation, overharvesting, overhunting, invasive species and pollution in addition to climate change — though the latter receives special attention because of its “global reach, ability to reshape entire ecosystems and potential to impact areas that are otherwise ‘protected.'”

To understand these threats, they modeled the effects of deforestation and climate change on the two critically endangered ruffed lemur species in the genus Varecia over the next century. “Because of their essential role as some of Madagascar’s last large-bodied seed dispersers and their sensitivity to habitat loss, ruffed lemurs serve as critical indicators of rainforest health,” says co-author Andrea Baden of Hunter College CUNY, New York. “Ruffed lemurs and rainforests rely on each other. Remove one and the system collapses.”

Undertaking what Morelli calls “a massive effort,” she and her 21 colleagues combined 88 years of data to report on how deforestation will affect ruffed lemurs. Morelli, who did her doctoral work in Madagascar, says team members conducted research at thousands of sites on this island off the southeast coast of Africa with a wide range of government, foundation and academic support.

They estimate that suitable rainforest habitat could be reduced by as much as 59 % from deforestation, as much as 75 % from climate change alone, and almost entirely lost from both before 2080. Thus, protecting protected areas is a key conservation strategy, research ecologist Morelli says. She and co-authors write, “Maintaining and enhancing the integrity of protected areas, where rates of forest loss are lower, will be essential for ensuring persistence of the diversity of the rapidly-diminishing Malagasy rainforests.”

Morelli adds, “Madagascar is facing devastating rates of forest loss, and lemurs are only found there and nowhere else. At this rate, even without climate change we’re going to lose the rainforest and its lemurs, but with climate change we’ll lose them even faster. If we can slow the deforestation, we can save some of them. Not all of them, but some of them.”

Morelli adds, “This is not just about Madagascar, though it’s a really special place, recognized as one of the world’s biodiversity hotspots, and people really care about it. But there is a broader message. This research reminds us that there are other threats to biodiversity. We show that deforestation continues to be an imminent threat to conservation.”

Baden says that the problem is not that people have not been trying to preserve habitat to save the lemurs. “There are already protected areas,” she says. “If we want to save habitat and species, in the face of climate change, we have to do a better job of enforcement. But even with well-enforced protected areas, the outlook is pretty grim.” The authors also discuss the likelihood that climate change will alter local residents’ ability to grow and gather food, perhaps forcing further encroachment on protected lands.

Overall, “We challenge the conservation community to contemplate what should be done if nearly all of Madagascar’s rainforest habitat were to be lost,” they write. “To date, most conservation on the island has focused on establishment of protected areas, but even these are being eroded, albeit at a slower rate. If protected areas are not able to serve their intended purpose, how can we ensure that the perpetuation of the richness of Madagascar’s biodiversity?”