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Meet CRISPR’s Younger Brother, SHERLOCK

One of CRISPR-cas9’s inventors has just announced the arrival of an inexpensive, portable diagnostic tool: SHERLOCK.

Image source: Mr Pics/Shutterstock

Along with Emmanuelle Charpentier and Jennifer Doudna, Feng Zhang is one of the inventors of CRISPR-cas9 — or “CRISPR" for short — the cut-and-paste method for editing evens that's taken genetics by storm. In fact, after a bruising legal battle, Zhang and the Broad Institute for which he works own the patent for the use of CRISPR in eukaryotes, at least for now. (His adversary in court, Doudna and UC Berkeley filed to appeal the verdict just last week.) That's a very sweet patent to own, since CRISPR become central to genetics research and therapies.

Now Zhang's back with a new acronym likely to become familiar in coming years. It's a diagnostic tool called the “Specific High Sensitivity Enzymatic Reporter Un LOCKing," or “SHERLOCK." And, yes, it is a sleuth of sorts, since it detects the presence nucleic acids belonging to disease-causing pathogens. He and 18 colleagues just published a paper in the journal Science announcing how they've found a new way to use CRISPR, as a diagnostic tool.

“In this diagnostic application we are really harnessing the power and diversity of biology" co-author Jim Collins told the Washington Post. “I view it as a potentially transformative diagnostic platform."

Unlike CRISPR-cas9, which works with a cas protein called “Cas 9," SHERLOCK works with a Cas relative discovered about a year ago, Cas 13a. It works with RNA, unlike Cas9, which targets DNA.

Zhang says that SHERLOCK will be an unusually mobile way of diagnosing disease due to its portability and low cost — he estimates it could cost as little as 61 cents per test. “We showed that this system is very stable, so you can really put it on a piece of paper and it will survive. You don't have to refrigerate it all the time," says Zhang. This would make it an ideal option in remote places lacking reliable electricity.

The Post asked professor of infectious diseases and preventive medicine at Vanderbilt William Schaffner, who was not involved in the research, for his reaction. ““My head is spinning a little bit because this looks very, very provocative. And exciting. If you had something that could be used as a screening test, very inexpensively and rapidly, that would be a huge advance, particularly if it could detect an array of infectious agents."

Patents for SHERLOCK have already been applied for, and team is ready now to move the detective out of the lab to clinical settings and the world.

To infectious disease researcher Scott Weaver the University of Texas, “It looks like one significant step on the pathway which is the Holy Grail, which is developing point-of-care, or bedside detection, which doesn't require expensive equipment or even reliable power."

Hulu's original movie "Palm Springs" is the comedy we needed this summer

Andy Samberg and Cristin Milioti get stuck in an infinite wedding time loop.

Gear
  • Two wedding guests discover they're trapped in an infinite time loop, waking up in Palm Springs over and over and over.
  • As the reality of their situation sets in, Nyles and Sarah decide to enjoy the repetitive awakenings.
  • The film is perfectly timed for a world sheltering at home during a pandemic.
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Two MIT students just solved Richard Feynman’s famed physics puzzle

Richard Feynman once asked a silly question. Two MIT students just answered it.

Surprising Science

Here's a fun experiment to try. Go to your pantry and see if you have a box of spaghetti. If you do, take out a noodle. Grab both ends of it and bend it until it breaks in half. How many pieces did it break into? If you got two large pieces and at least one small piece you're not alone.

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Our ‘little brain’ turns out to be pretty big

The multifaceted cerebellum is large — it's just tightly folded.

Image source: Sereno, et al
Mind & Brain
  • A powerful MRI combined with modeling software results in a totally new view of the human cerebellum.
  • The so-called 'little brain' is nearly 80% the size of the cerebral cortex when it's unfolded.
  • This part of the brain is associated with a lot of things, and a new virtual map is suitably chaotic and complex.

Just under our brain's cortex and close to our brain stem sits the cerebellum, also known as the "little brain." It's an organ many animals have, and we're still learning what it does in humans. It's long been thought to be involved in sensory input and motor control, but recent studies suggests it also plays a role in a lot of other things, including emotion, thought, and pain. After all, about half of the brain's neurons reside there. But it's so small. Except it's not, according to a new study from San Diego State University (SDSU) published in PNAS (Proceedings of the National Academy of Sciences).

A neural crêpe

A new imaging study led by psychology professor and cognitive neuroscientist Martin Sereno of the SDSU MRI Imaging Center reveals that the cerebellum is actually an intricately folded organ that has a surface area equal in size to 78 percent of the cerebral cortex. Sereno, a pioneer in MRI brain imaging, collaborated with other experts from the U.K., Canada, and the Netherlands.

So what does it look like? Unfolded, the cerebellum is reminiscent of a crêpe, according to Sereno, about four inches wide and three feet long.

The team didn't physically unfold a cerebellum in their research. Instead, they worked with brain scans from a 9.4 Tesla MRI machine, and virtually unfolded and mapped the organ. Custom software was developed for the project, based on the open-source FreeSurfer app developed by Sereno and others. Their model allowed the scientists to unpack the virtual cerebellum down to each individual fold, or "folia."

Study's cross-sections of a folded cerebellum

Image source: Sereno, et al.

A complicated map

Sereno tells SDSU NewsCenter that "Until now we only had crude models of what it looked like. We now have a complete map or surface representation of the cerebellum, much like cities, counties, and states."

That map is a bit surprising, too, in that regions associated with different functions are scattered across the organ in peculiar ways, unlike the cortex where it's all pretty orderly. "You get a little chunk of the lip, next to a chunk of the shoulder or face, like jumbled puzzle pieces," says Sereno. This may have to do with the fact that when the cerebellum is folded, its elements line up differently than they do when the organ is unfolded.

It seems the folded structure of the cerebellum is a configuration that facilitates access to information coming from places all over the body. Sereno says, "Now that we have the first high resolution base map of the human cerebellum, there are many possibilities for researchers to start filling in what is certain to be a complex quilt of inputs, from many different parts of the cerebral cortex in more detail than ever before."

This makes sense if the cerebellum is involved in highly complex, advanced cognitive functions, such as handling language or performing abstract reasoning as scientists suspect. "When you think of the cognition required to write a scientific paper or explain a concept," says Sereno, "you have to pull in information from many different sources. And that's just how the cerebellum is set up."

Bigger and bigger

The study also suggests that the large size of their virtual human cerebellum is likely to be related to the sheer number of tasks with which the organ is involved in the complex human brain. The macaque cerebellum that the team analyzed, for example, amounts to just 30 percent the size of the animal's cortex.

"The fact that [the cerebellum] has such a large surface area speaks to the evolution of distinctively human behaviors and cognition," says Sereno. "It has expanded so much that the folding patterns are very complex."

As the study says, "Rather than coordinating sensory signals to execute expert physical movements, parts of the cerebellum may have been extended in humans to help coordinate fictive 'conceptual movements,' such as rapidly mentally rearranging a movement plan — or, in the fullness of time, perhaps even a mathematical equation."

Sereno concludes, "The 'little brain' is quite the jack of all trades. Mapping the cerebellum will be an interesting new frontier for the next decade."

Economists show how welfare programs can turn a "profit"

What happens if we consider welfare programs as investments?

A homeless man faces Wall Street

Spencer Platt/Getty Images
Politics & Current Affairs
  • A recently published study suggests that some welfare programs more than pay for themselves.
  • It is one of the first major reviews of welfare programs to measure so many by a single metric.
  • The findings will likely inform future welfare reform and encourage debate on how to grade success.
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Unhappy at work? How to find meaning and maintain your mental health

Finding a balance between job satisfaction, money, and lifestyle is not easy.

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