Category Archives: Biology

Biology

Soft-landing methods aim to simplify structural biology – Nature.com

A mass spectrometer modified by Stephan Rauschenbachs team reduces damage to proteins so they can be used in cryo-electron microscopy.Credit: Tim Esser

In his lecture after winning a share of the 2002 Nobel Prize in Chemistry, John Fenn described his work as creating wings for molecular elephants.

Fenn pioneered the use of a method called electrospray ionization (ESI) to make intact proteins among natures beefiest biomolecules literally fly, transferring them from complex mixtures into gases and then into mass spectrometers for extensive analysis. Alongside the research of co-recipient Koichi Tanaka, Fenns work1 made it possible for scientists to dive deep into the chemical composition and therefore the sequences, chemical modifications and molecular partners of whole proteins, using mass spectrometry.

Such data can be invaluable for basic research and biopharmaceutical development but not protein-structure determination. A growing number of researchers, however, are enthusiastic about the idea of hooking up the technique to a technology that can fill that gap. Using ESI mass spectrometry as an air traffic control system to facilitate the take-off, flight and gentle touchdown of intact proteins, in preparation for state-of-the-art methods such as cryo-electron microscopy (cryo-EM), could greatly expand the range of protein structures that can be solved with these powerful but finicky methods. Yet whether its possible to land Fenns winged molecular elephants safely has remained unclear.

Catching proteins at play: the method revealing the cells inner mysteries

Much excitement, therefore, accompanied an August preprint2 from researchers led by physical chemist Stephan Rauschenbach at the University of Oxford, UK. It presented a near-atomic-resolution cryo-EM structure for the enzyme -galactosidase after preparation with a mass-spectrometry-based approach known as electrospray ion-beam deposition (ES-IBD). The sugar-metabolizing enzyme is one of the best-characterized proteins, making it an ideal test bed for whether soft landing mass-spectrometry methods such as ES-IBD can deliver the goods. By tuning the acceleration of a protein as it travels through the mass spectrometer, soft-landing methods aim to limit the force with which the protein arrives at its final destination, thereby minimizing the resulting damage. Everybody can get a good structure of -galactosidase but not after taking it through a mass spectrometer, landing it and visualizing it, says chemist Carol Robinson, who collaborated with Rauschenbach and is also at the University of Oxford.

The researchers results revealed a protein that was somewhat crumpled and dehydrated, but that still closely resembled conventional cryo-EM structures. A July preprint3 from a team led by biomolecular chemist Joshua Coon and structural biologist Timothy Grant, both at the University of WisconsinMadison, also reported natural-looking albeit moderate-resolution cryo-EM structures for multiple proteins.

Enthusiasts see the possibility of a facile sample-preparation method that allows researchers to generate near-atomic-resolution protein structures with unprecedented precision and efficiency. It has the potential to be the default way people prepare samples for cryo-EM, says Coon. Other modes of structural analysis could also benefit, including single-molecule methods that actively monitor the dynamics of flexible proteins. But few groups have made headway with soft-landing mass spectrometry, and the promising results that have been obtained are insufficient to allay concerns that proteins reaching the microscope do not fully retain their natural structure. Its a very exciting subfield, concludes Alexis Rohou, a structural biologist at the biotechnology firm Genentech in South San Francisco, California. But there are many, many things yet to be overcome.

The marriage of ESI mass spectrometry and cryo-EM is the product of difficulties in two fields.

Native protein analysis with ESI mass spectrometry entails ejecting proteins from a liquid environment to form airborne gas phase particles in a vacuum. This allows researchers to study the biochemical characteristics of intact proteins, as opposed to smaller chunks called peptides, but whether protein structures are fundamentally disrupted by this transition has been the subject of a long-standing debate.

People were saying to me, You cant really believe that this looks anything like it does in crystallography or in electron microscopy surely being in the gas phase has ruined the structure to some extent, says Robinson, a specialist in native mass spectrometry. She was convinced otherwise, however, and early experiments supported her view. In 2003, for instance, chemist R. Graham Cooks and his colleagues at Purdue University in West Lafayette, Indiana, generated arrays of soft-landed enzymes that remained functional despite their arduous journey4. Around a decade later, Robinsons team used transmission electron microscopy (TEM) to show that the structural features of well-studied protein complexes were generally preserved after soft-landing mass spectometry5.

A reconstruction of the -galactosidase enzyme after soft-landing mass spectrometry.Credit: Colin Hemme

TEM is not suitable for defining the structure of protein molecules at high resolution, but cryo-EM is. In cryo-EM, large numbers of protein molecules are trapped in a thin layer of glass-like ice on a sample grid under conditions that preserve their fine structural features. These frozen protein molecules are imaged at different angles, and then the images are computationally reconstructed into a 3D shape. A good cryo-EM experiment can reveal protein structures with atomic resolution, and the method is now a mainstay of structural biology, with more than 15,000 structures deposited in the worlds repository for protein structures: the Protein Data Bank.

But cryo-EM users have a struggle of their own: sample preparation. At least half the time, you just cant get it to work, says Grant. And for certain proteins, its all the time. At the freezing stage, protein specimens exist in a thin film of solution that leaves them exposed to air, which can induce protein unfolding and degradation, Grant says. This airwater interface can also cause proteins to preferentially adopt specific orientations. Without a diversity of orientations, it becomes impossible to generate a high-quality cryo-EM reconstruction. Soft-landing mass spectrometry could help to eliminate that bias.

Furthermore, by including soft-landing mass spectrometry in the earliest stages of sample preparation, cryo-EM users could spare themselves the trouble of purifying their proteins and instead pluck them directly from samples on the basis of the proteins size and biochemical characteristics. Maybe you could amplify a single population and only deposit that on a grid, or only deposit that in one region of the grid so that another region has proteins in a different state, says biochemist James Evans, who is part of the leadership team for the Pacific Northwest Cryo-EM Center in Portland, Oregon.

The successful integration of soft-landing mass spectrometry with cryo-EM could therefore resolve two pressing issues the gas-phase controversy and protein-sample preparation at a stroke. But getting to that point has proved harder than expected.

With any aerial routine, one of the biggest challenges is to make a perfect landing and so it was with soft-landing mass spectrometry. We started more than 20 years ago, recalls Klaus Kern, a chemist at the Max Planck Institute for Solid State Research in Stuttgart, Germany, who supervised Rauschenbachs initial work on ES-IBD as a postdoc. It took 1012 years before it really started working.

The instrumentation itself can be built around a commercial mass spectrometer both Coon and Rauschenbach have used Orbitrap instruments, from US biotechnology company Thermo Fisher Scientific, as a foundation. But considerable tuning and modification are required to protect the integrity of the protein molecule during transit and to manage its speed and eventual impact with the sample grid. Careful optimization of both the sample-preparation conditions and the surface of the landing pad are also required.

Coon recalls reaching out to Grant early in their collaboration to show off some of the data his team had produced. We were all proud of these images, and we said, Tim, what do you think? And hes like, Your proteins are shit, they look kind of like you threw a tomato at a wall, Coon says. His team spent about 18 months testing different instrumentation and sample and surface conditions before finding a formula that worked: coating sample grids with an ultra-thin layer of glycerol to capture the landed proteins. Using TEM, the researchers confirmed successful deposition of seemingly intact GroEL a cylindrical chaperone protein that enables the folding of other proteins with modest resolution. But the workflow was incompatible with cryo-EM, because glycerol produces too much noise in the images, and so they went back to the drawing board to make their process more cryo-friendly. The results were published in April 20226.

Months later, Rauschenbach and his colleagues described an approach that came closer to a standard cryo-EM workflow7. They deposited gas-phase proteins onto a room-temperature, unmodified grid, which they then plunged into liquid nitrogen to freeze the proteins in place without forming an ice layer. Rauschenbach was pleased to note that the structure of -galactosidase looked more or less correct, and his team saw evidence of features such as -helices and -sheets. Even at room temperature, something was retained, he says. But the resolution was not good enough to fit models.

The entire protein universe: AI predicts shape of nearly every known protein

Rauschenbach and Coon independently realized that freezing the proteins as soon as they leave the vacuum environment of the mass spectrometer could solve that problem. Both teams described important progress towards the use of soft-landing mass spectrometry for cryo-EM sample preparation in the July and August preprints2,3. Coon and Grants group achieved3 this by landing the proteins on a grid that it had pre-chilled to 190C. The researchers then restored the grid to atmospheric pressure before plunging it into liquid nitrogen. By contrast, Rauschenbachs team coated its mass-spectrometry-deposited proteins with a thin ice layer by introducing low levels of water vapour into the sample chamber, which quickly froze on the surface of the pre-chilled grid2. Rauschenbach says that his teams ice-free samples tend to form problematic artefacts, but when you embed them in ice, you get the structure.

The results have led to cautious optimism. Both groups saw considerable improvements in the resolution that they could obtain for -galactosidase, and Coons group also obtained a higher-quality 3D structure for GroEL compared with the earlier work using glycerol. In fact, Rauschenbach and his colleagues achieved a resolution of 2.6 ngstrms about the length of a hydrogen bond, and slightly poorer than results obtained with conventional cryo-EM samples.

But his teams reconstruction of -galactosidase was somewhat compacted relative to the proteins known structure. The researchers surmised that the enzymes journey through a harsh vacuum environment stripped away the water molecules that surround proteins in nature, causing it to dehydrate and shrivel. The important point is [that] this is not the solution structure it is a gas-phase protein landing on a cold surface, Rauschenbach explains. In their preprint, the researchers showed that they could largely restore the correct structure using an algorithm that simulates protein hydration.

The significance of this dehydration for sample preparation is unclear. On the one hand, these results largely vindicate researchers such as Robinson, who posited that gas-phase proteins generally retain their structure. On the other hand, structural biologists seeking a route for preparing intact native proteins are still awaiting more evidence. How much dehydration damages the protein is, I think, a somewhat open question, says Grant. He and his team are continuing to test other proteins in their workflow Coon says that they prepare four to five new grids daily in the hope that they can improve understanding of what happens during the soft-landing mass-spectrometry process.

But Tanmay Bharat, a structural biologist at the MRC Laboratory of Molecular Biology in Cambridge, UK, who collaborated with Rauschenbach, is optimistic about the method already. Its a very good starting point for improving the process even more, he says, although he notes that further work will be required to turn it into a robust and generalizable protocol for protein cryo-EM. Both teams are looking into opportunities to use mass spectrometry with proteins that retain at least a partial water coating and can therefore be frozen in a more natural state.

Biomolecular chemist Joshua Coon (right) and his team spent 18 months optimizing equipment and conditions for soft-landing mass spectrometry.Credit: David Nevala

Other groups have begun testing the waters of soft-landing mass-spectrometry. For example, Rohou and his colleagues at Genentech are working with an ion mobility deposition method developed by life-science company IonDx in Monterey, California, which allows the sorting of proteins that remain fully hydrated and therefore could retain more native structures. The team still struggles to land intact proteins on its grids, says Rohou, but they have frozen water and protein in them, and we can recognize proteins in each individual droplet.

Similarly, Evans and his collaborator Ljiljana Paa-Toli, a mass-spectroscopy specialist at Pacific Northwest National Laboratory in Richland, Washington, who have also stumbled with soft-landing mass spectrometry, are exploring an alternative approach. Known as Structures for Lossless Ion Manipulation (SLIM), it operates under softer vacuum conditions and could therefore reduce the loss of water. Youre still under some vacuum, but you may be able to create and keep a shell of hydration or a salt shell even around the protein, says Evans.

For cryo-EM enthusiasts, the current state of limbo is both exciting and frustrating. Its almost like its binary you can either do it all or do nothing, says Grant. And right now, nobodys done it all. And the consequences of turning this into a robust, lab-ready technique could be huge.

The must-have multimillion-dollar microscopy machine

Integrated into the cryo-EM workflow, soft-landing mass spectrometry could allow more-elaborate experiments. You could lyse a cell and basically pick out complexes of certain molecules with certain other molecules, says Bharat, or more precisely characterize the interactions between drug candidates and target proteins. The integration could also make small proteins more amenable to cryo-EM analysis. Such proteins are typically invisible in the relatively thick layers of ice formed by current plunge-freezing methods, Rohou explains. A mass-spectrometry-based method that either eliminates the need for ice or reduces it to a thin shell around the protein could make these proteins tractable for high-resolution analysis.

But soft-landing mass spectrometry is already creating exciting possibilities for protein analysis at the single-molecule level. Kern, Rauschenbach and their colleagues initially began exploring soft-landing mass spectrometry as a preparative tool for characterizing proteins and other biomolecules with an approach called scanning tunnelling microscopy (STM). This involves a tiny, ultrasharp probe being manoeuvred over an immobilized sample while a voltage is applied; bumps and divots in the sample surface produce changes in the resulting current, which can then be mapped to determine the underlying sample structure. In 2020, Kern and his colleagues demonstrated for the first time that STM could reveal the structure of complex carbohydrates that had been deposited by soft-landing mass spectrometry8. His team is now extending the approach to analyse glycoproteins in unprecedented detail. We can directly see what glycan is attached to what amino acid in a polypeptide, says Kern.

Kerns team is also integrating soft-landing mass spectrometry with a relatively obscure STM variant known as low-energy electron holography (LEEH), to recover information about flexible proteins that can adopt multiple conformations. In LEEH, the ultrasharp probe serves as an electron source that bombards a target molecule on an ultraclean layer of graphene, producing an interference pattern that can be reconstructed to determine the targets 3D structure. Theoretically, the process can achieve near-atomic resolution, Kern notes. But his team has already clearly distinguished different structural configurations of a protein of interest a scenario that would create only blurry images in cryo-EM9.

These developments are just the beginning for soft-landing mass spectrometry, and for Rauschenbach, thats the most exciting aspect: the untapped versatility. You can do all types of chemistry, deposition and analysis methods, he says. We can use it for so many things.

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Soft-landing methods aim to simplify structural biology - Nature.com

Biology

Nightwing Secretly Has 1 Superpower (Because Alfred Messed with His Biology) – Screen Rant

Nightwing, much like the majority of the Bat-Family, is held in high regard for his status as a non-meta hero, making him one of the most formidable and esteemed heroes in the DC universe, despite lacking superhuman abilities. However, it has come to light that Nightwing possesses a unique superpower, which distinguishes him from all others, and it's all thanks to his loyal butler and grandfather figure, Alfred Pennyworth.

Battle for the Cowl #3 written by Tony Daniel made it strikingly clear that Nightwing possesses a unique resistence to the fear toxin used by infamous supervillain Scarecrow.

As it turns out, Nightwing's exceptional immunity to fear gas was granted to him through Alfred's meticulous inoculation of the Boy Wonder against every known variant of this hallucinogenic drug.

Related: Scarecrow Works Much Better as Nightwing's Villain Than Batman's

Within the daunting landscape of Gotham City, Nightwing, and the Bat-Family confront an endless array of nightly threats, many of which stem from Batman's notorious Rogues Gallery. Among these iconic adversaries, few can induce as much spine-chilling dread as Scarecrow. Armed with his infamous 'fear toxin,' a potent hallucinogenic concoction of his own creation, Scarecrow immerses his victims in their darkest nightmares, subjecting them to unparalleled terror. It's a nightmarish weapon that strikes fear into the hearts of even the bravest souls. Nevertheless, Nightwing's unique superpower enables him to confront the fear toxin in a manner distinct from any other hero or villain.

This remarkable resistance to fear-inducing substances becomes strikingly evident in a memorable scene from Battle for the Cowl #3, when Nightwing finds himself unwittingly dosed with fear gas by Red Hood, the once-second Robin. However, the potent fear agent proves utterly ineffective against him, causing, at most, a hint of disorientation. This remarkable immunity is effectively Nightwing's overlooked 'superpower,' the envy of every Gotham citizen. Dick Grayson's immunity to fear gas grants him a distinct advantage. While most individuals would find themselves entirely incapacitated when exposed to fear gas, a substance known for its debilitating and, sometimes lethal effects, Dick has repeatedly demonstrated his imperviousness to its influence.

Alfred inoculating Dick against fear gas may have been a boon for the hero in the long run, and the hero community for that matter, but it does call into question the ethics of Alfreds decision, since this was most likely done during Dicks Robin years, where he would have been still just a boy, and couldnt have given proper consent. As apparent in Battle for the Cowl # 3, Nightwing doesnt hold this against Alfred, since he mentions the tampering to his biology in a nonchalant and positive context, but it still is a decision made on Pennyworth's part that may not have been one of his most ethical.

This extraordinary resilience is vividly showcased in Nightwing Vol. 4 #56 by Scott Lobdell, Fabian Nicieza, and Davide Gianfelice, during the 'Ric' storyline. In an encounter with Scarecrow, the villain doses the vigilante with the toxin; Dick Grayson remains utterly unaffected. This unique ability has the potential to be a pivotal factor in future storylines, where the tide of a crisis involving fear gas could be shifted by Dick's exceptional immunity. In such scenarios, Nightwing may emerge as the sole hero capable of saving the day, highlighting the profound significance of his immunity in the face of perilous encounters with this menacing hallucinogenic substance.

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Nightwing Secretly Has 1 Superpower (Because Alfred Messed with His Biology) - Screen Rant

Biology

Missing ‘Law of Nature’ Found That Describes The Way All Things Evolve – ScienceAlert

Complex, evolving systems abound in our Universe, even beyond the realms of biology. From the growth of stars to prebiotic chemistry, diverse mixes of materials can often be shaped into far more complex forms.

Yet unlike other so many other physical phenomena, their changing nature is yet to be represented by a discrete law.

That's according to a US team of astrobiologists, philosophers, a mineralogist, a theoretical physicist, and a data scientist who describe the "missing law" of nature in an intriguing new peer-reviewed paper.

"Given the ubiquity of evolving systems in the natural world, it seems odd that one or more laws describing their behaviors have not been more quickly forthcoming," the authors write.

The team's own "law of increasing functional information" says evolution in all its forms inevitably leads to more patterning, diversity, and complexity in natural complex systems.

Evolution is certainly not unique to Earth's biosphere; it takes place in other extremely complex systems, such as our Solar System, stars, atoms, and minerals.

"The Universe generates novel combinations of atoms, molecules, cells, etc," says first author of the study, astrobiologist Michael Wong from Carnegie Institution for Science in Washington, DC.

"Those combinations that are stable and can go on to engender even more novelty will continue to evolve. This is what makes life the most striking example of evolution, but evolution is everywhere."

The paper describes how just hydrogen and helium the two most abundant elements at the time of the Big Bang coalesced to form the first stars. By the time a star reaches the end of its life it can generate more than 100 elements with around 2000 varieties of isotope.

On Earth, an enormous diversity of mineral 'species' were created from simple beginnings as the planet formed across 4.55 to 2.5 billion years ago. There are now more than 5,900 known mineral species on Earth, which became increasingly chemically complex as emerging forms of life released oxygen into the atmosphere.

Iron's reaction with oxygen-based minerals ushered in a new era in ancient life and laid the groundwork for our own evolution in tandem with other minerals.

The complexity of Earth's surface mineralogy grew further as life evolved from single-celled to multicellular organisms and ecosystems formed. The wide range of minerals that were formed changed the course of evolution and its options.

Biological and mineral systems continually interact to influence each other's diversity, and life as we know it is the result of this interaction.

"These evolving systems appear to be conceptually equivalent in that they display three notable attributes," the authors write.

"1) They form from numerous components that have the potential to adopt combinatorially vast numbers of different configurations; 2) processes exist that generate numerous different configurations; and 3) configurations are preferentially selected based on function."

So, is there something in the way information can be transferred that accounts for the shared characteristics of seemingly diverse evolving systems? Could there be a universal basis for selection? The team thinks both answers are yes.

"An important component of this proposed natural law is the idea of 'selection for function,'" says Wong.

According to Darwin, an organism's primary function in the context of biology is to ensure its own survival long enough to reproduce successfully. The team says this new proposal broadens our understanding by pointing out the existence of three distinct types of function in the natural world.

The most fundamental function we could call 'static persistence' maintenance of stable atomic or molecular arrangements.

'Dynamic persistence' describes how systems that are dynamic and have access to constant sources of energy are also more likely to endure.

And lastly, 'novelty generation' refers to the propensity of evolving systems to generate novel configurations, which can result in surprising novel behaviors or characteristics.

Wong and team point out that physical laws of motion, gravity, electromagnetism, and thermodynamics govern the functions of macroscopic natural systems across space and time. So it makes sense that we should have a law of nature for evolution.

"An asymmetric trajectory based upon functionality may seem antithetical to scientific analysis," the team concludes.

"Nevertheless, we conjecture that selection based on static persistence, dynamic persistence, and novelty generation is a universal process that results in systems with increased functional information."

The study has been published in Proceedings of the National Academy of Sciences.

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Missing 'Law of Nature' Found That Describes The Way All Things Evolve - ScienceAlert

Biology

OSU Mortar Board names 2023 Top 20 freshmen men and women – Oklahoma State University

Monday, October 16, 2023

Media Contact: Sydney Trainor | Communications Specialist | 405-744-9782 | sydney.trainor@okstate.edu

The Oklahoma State University chapter of the Mortar Board honor society recently named students to its annual list of Top 20 Freshmen Men and Top 20 Freshmen Women, as well as Top 10 Freshmen Men and Women for the 2022-23 class.

"Mortar Board is a national honor society recognizing college seniors for their exemplary scholarship, leadership and service, said Sarah Easterly, Mortar Board Top 10 Freshmen coordinator. The Top 20 award is based off the student's application, and the Top 10 award is based off an interview process. Mortar Board was highly impressed with the 153 applicants we had this year."

Students selected for the honor are chosen based on scholarship, outstanding leadership and community service. Students apply in their sophomore year based on achievement during their first year in college. The Top 10 men and women were recognized Oct. 14 during the OSU-Kansas football game at Boone Pickens Stadium.

*Audrey Bishop Plant and Soil Science Van Alstyne, Texas

*Virginia Buller Elementary Education Turpin, Oklahoma

*Callie Conyers Nutritional Sciences/Pre-Med Gruver, Texas

Camdyn Cook Nutritional Sciences/Pre-Med Healdton, Oklahoma

*Kate Dillon Nutritional Sciences Mustang, Oklahoma

*Katie Dillon Agribusiness Louisburg, Kansas

Hattie Howell Microbiology, Cell and Molecular Biology/Pre-Med Tulsa

*Tatumn Kennedy Biosystems Engineering Meeker, Colorado

Macy Koch Biochemistry and Molecular Biology Perry, Oklahoma

*Katon Lunsford Strategic Communications Kingfisher, Oklahoma

Sydney Martens Marketing Fairview, Oklahoma

Taylor McConnell Animal Science Wellston, Oklahoma

*Emily Myrick Communication Sciences and Disorders Mineral Wells, Texas

Presley Pullen Agricultural Communications and Animal Science Stratford, Oklahoma

Kayman Ross Biology Premedical Sciences and Biochemistry Choctaw, Oklahoma

Rylee Smith Agricultural Education and Agricultural Communications Oologah, Oklahoma

*Regan Smithwick Animal Science Miles, Texas

*Lily Stuckey Psychology Tulsa

Chenoa Turtle Biology and Physiology/Pre-Med Park Hill, Oklahoma

Sophie Varner Agribusiness and Agricultural Communications Bristow, Oklahoma

Brooks Beck Biology/Pre-Med Texarkana, Texas

Caleb Blackwell Agricultural Economics Amarillo

*Trevor Friesen Management, Marketing and International Business Edmond, Oklahoma

*Eli Greenlee Agribusiness Prague, Oklahoma

*Cade Harris Animal Science/Pre-Vet Brock, Texas

Adam Hartman Biosystems Engineering Paris, Texas

*Jason Heath Applied Exercise Science Paris, Texas

*Caleb Horne Agricultural Economics Stillwater

Peyton Hughes Finance Enid, Oklahoma

*Justis James Nutritional Sciences/Pre-Med Eufaula, Oklahoma

*Jace Johnson Architecture Saint Jo, Texas

Brenden Kienholz Finance and Economics Emporia, Kansas

*Kelton O'Neil Finance Alva, Oklahoma

William Penney Industrial Engineering and Management Coalgate, Oklahoma

Austin Reed Business Management Freedom, Oklahoma

Kaden Slater Finance Alva, Oklahoma

*Spencer Smith Entrepreneurship/Pre-Law Miami, Oklahoma

Reed Stout Biology Muskogee, Oklahoma

*Michael Tate Strategic Communications and Political Science Florence, Mississippi

Will Trachte Chemistry Lawton, Oklahoma

* - Top 10

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OSU Mortar Board names 2023 Top 20 freshmen men and women - Oklahoma State University

Biology

Robert Sapolsky Doesn’t Believe in Free Will. (But Feel Free to … – The New York Times

There is no free will, according to Robert Sapolsky, a biologist and neurologist at Stanford University and a recipient of the MacArthur Foundation genius grant. Dr. Sapolsky worked for decades as a field primatologist before turning to neuroscience, and he has spent his career investigating behavior across the animal kingdom and writing about it in books including Behave: The Biology of Humans at Our Best and Worst and Monkeyluv, and Other Essays on Our Lives as Animals.

In his latest book, Determined: A Science of Life Without Free Will, Dr. Sapolsky confronts and refutes the biological and philosophical arguments for free will. He contends that we are not free agents, but that biology, hormones, childhood and life circumstances coalesce to produce actions that we merely feel were ours to choose.

Its a provocative claim, he concedes, but he would be content if readers simply began to question the belief, which is embedded in our cultural conversation. Getting rid of free will completely strikes at our sense of identity and autonomy and where we get meaning from, Dr. Sapolsky said, and this makes the idea particularly hard to shake.

There are major implications, he notes: Absent free will, no one should be held responsible for their behavior, good or bad. Dr. Sapolsky sees this as liberating for most people, for whom life has been about being blamed and punished and deprived and ignored for things they have no control over.

He spoke in a series of interviews about the challenges that free will presents and how he stays motivated without it. These conversations were edited and condensed for clarity.

To most people, free will means being in charge of our actions. Whats wrong with that outlook?

Its a completely useless definition. When most people think theyre discerning free will, what they mean is somebody intended to do what they did: Something has just happened; somebody pulled the trigger. They understood the consequences and knew that alternative behaviors were available.

But that doesnt remotely begin to touch it, because youve got to ask: Where did that intent come from? Thats what happened a minute before, in the years before, and everything in between.

For that sort of free will to exist, it would have to function on a biological level completely independently of the history of that organism. You would be able to identify the neurons that caused a particular behavior, and it wouldnt matter what any other neuron in the brain was doing, what the environment was, what the persons hormone levels were, what culture they were brought up in. Show me that those neurons would do the exact same thing with all these other things changed, and youve proven free will to me.

So, whether I wore a red or blue shirt today are you saying I didnt really choose that?

Absolutely. It can play out in the seconds before. Studies show that if youre sitting in a room with a terrible smell, people become more socially conservative. Some of that has to do with genetics: Whats the makeup of their olfactory receptors? With childhood: What conditioning did they have to particular smells? All of that affects the outcome.

What about something bigger, like choosing where to go to college?

You ask, Why did you pick this one? And the person says, Ive learned that I do better in smaller classes. Or, They have an amazing party scene. At any meaningful juncture, were making decisions based on our tastes and predilections and values and character. And you have to ask: Where did they come from?

Neuroscience is getting really good at two levels of stuff. One is understanding what a particular part of the brain does, based on techniques like neuroimaging and transcranial magnetic stimulation.

The other is at the level of tiny, reductive stuff: This variant of this gene interacts with this enzyme differently. So, we kind of understand what happens in one neuron. But how do 30 billion of them collectively make this a human cortex instead of a primate cortex? How do you scale up from understanding little component parts and getting some sense of the big, emergent thing?

Say we figured that out. Have X happen 4,000 times per second in Y part of the brain, countered as an opposing, inhibitory thing 2,123 times a second when the hormone levels are doing such-and-such. How does this big thing called a behavior or a personality or a thought or a mistake pop out at the macro level? Were beginning to understand how you get from one level to the other, but its unbelievably difficult.

If were not responsible for our actions, can we take ownership of them?

Well, we can take ownership in a purely mechanical sense. My molecules knocked into the molecules making up that vase of flowers and knocked it over and broke it thats true. And we can keep ourselves going with myths of agency when it really doesnt make a difference. If you want to believe that you freely chose to floss your upper teeth before your bottom teeth today, thats a benign myth to operate with.

But youre saying that the myth isnt always benign?

Fundamentally injurious things about our universe run on the notion that people get stuff that they didnt earn or they didnt deserve, and a huge amount of humanitys misery is due to myths of free will.

Most of the time, I get by without having to pay any attention whatsoever to how I think things work. Recognize how hard it is to do otherwise. Save that recognition for when it matters: when youre on a jury; when youre a schoolteacher, assessing students. If you have myths about free will, keep it to how youre flossing your teeth.

I want to wean people off the knee-jerk reaction to the notion that without free will, we will run amok because we cant be held responsible for things. That we have no societal mechanisms for having dangerous people not be dangerous, or for having gifted people do the things society needs to function. Its not the case that in a deterministic world, nothing can change.

How should privileged people think about their accomplishments?

Every living organism is just a biological machine. But were the only ones that know that were biological machines; we are trying to make sense of the fact that we feel as if our feelings are real.

At some point, it doesnt make a difference whether your feelings are real or whether your feeling of feelings being real is the case. We still find things aversive enough as biological machines that its useful to call stuff like that pain or sadness or unhappiness. And even though its completely absurd to think that something good can happen to a machine, its good when the feeling of feeling pain is lessened.

Thats a level on which we have to function. Meaning feels real. Purpose feels real. Every now and then, our knowledge of the machine-ness should not get in the way of the fact that this is a weird machine that feels as if feelings are real.

Do we lose love, too, if we lose free will?

Yeah. Like: Wow! Why? Why did this person turn out to love me? Where did that come from? And how much of that has to do with how my parents raised me, or what sort of olfactory receptor genes I have in my nose and how much I like their scent? At some point you get to that existential crisis of, Oh God, thats whats underlying all this stuff! Thats where the machine-ness becomes something we should be willing to ignore.

But its not OK for you to decide, with the same denial of reality, that you truly deserve a better salary than the average human on this planet.

Do it for where its needed. I sure cant do it more than a tiny percent of the time. Like once every three and a half weeks or so. Its a confusing, recursive challenge to watch yourself watching yourself, and to decide that what youre feeling feels real.

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Robert Sapolsky Doesn't Believe in Free Will. (But Feel Free to ... - The New York Times

Biology

Natural Selection Surprises: Evolutionary Lessons From the Wild Lizards of Florida – SciTechDaily

New research provides fresh insights into evolutionary stasis by studying the survival patterns of lizards in their natural habitat. Contrary to traditional beliefs, the study found that natural selection, which maintains an average species feature, was infrequent. Instead, it revealed that traits advantageous for survival varied from year to year, yet overall, species appearance remained largely unchanged over time.

Long-term lizard observation challenges the conventional understanding of natural selection, suggesting species can remain consistent in appearance while still undergoing evolution.

Many species experience little to no change over long periods of time. Biologists often fall back on the same explanation for why this is true: that natural selection favors individuals with more moderate characteristics. Individuals with more extreme features longer limbs, for example have a disadvantage, while more moderate or average individuals are more likely to survive and reproduce, passing on their common features.

However, new research from Washington University in St. Louis and the Georgia Institute of Technology provides a more complete explanation of how evolution plays out among species that live side-by-side. By directly measuring the long-term survival of lizards in the wild, the scientists showed that co-existing species each occupy a distinct fitness peak that is best understood as part of a communitywide fitness surface or landscape.

The study, led by James Stroud at Georgia Tech and published this week in the Proceedings of the National Academy of Sciences, offers a new way of thinking about how species relate to each other over time and how the differences between them reinforce their distinctness.

Taking high-resolution photographs of lizard feet to measure the size of adhesive sub-digital toepads. Credit: Days Edge Prod

Jonathan Losos, the William H. Danforth Distinguished University Professor and a professor of biology in Arts & Sciences at Washington University, said: If species are adapted to their environment, and the environment doesnt change, then you wouldnt expect the species to change. However, when scientists have gone out and studied natural selection, they rarely find evidence of such stabilizing selection.

Given this disconnect, we set out to study natural selection on the organisms we know so well,Anolislizards, to measure selection over several years and try to understand whats going on, Losos said.

Stroud, who was working as a postdoctoral researcher in Losos lab at WashU at the time, identified a place where four different species of anoles were living together on a small island in a lake in theFairchild Tropical Botanical Gardennear Miami.

He caught thousands of individual lizards on the island, tagged them, and measured their body proportions. Stroud then re-caught all of the lizards on the island every six months for 2 years, a period of time representing two to three generations of lizards.

James Stroud uses a tiny lasso attached to a fishing pole to catch a lizard. Credit: Days Edge Prods

New lizards that showed up were island babies, obviously. If a lizard disappeared from his census rolls, it was safe for Stroud to assume it had died, because the surrounding lake, filled with predatory fish, didnt let them leave. By determining which lizards survived from one year to the next, the researchers could evaluate whether survival was related to the body traits they had been measuring, like leg length.

What is special about this study is that we simultaneously measured natural selection on four co-existing species, something that has rarely been accomplished, said Losos, who also serves as the director of theLiving Earth Collaborative. By coincidence, just as our paper was published, another group published a similar study on Darwins famous finches of the Galapagos Islands.

In the Florida lizards, Losos and Stroud found that the stabilizing form of natural selection that which maintains a species same, average features was extremely rare. In fact, natural selection varied massively through time. In some years, lizards with longer legs would survive better, and in other years, lizards with shorter legs fared better. At other times, there was no clear pattern at all.

The most fascinating result is that natural selection was extremely variable through time, Stroud said. We often saw that selection would completely flip in direction from one year to the next. When combined into a long-term pattern, however, all this variation effectively canceled itself out: species remained remarkably similar across the entire time period.

Scientists do not yet fully understand how evolution works on the community level. There are very few long-term studies like this one because of the great amount of work and time required.

Evolution can and does happen its this ongoing process, but it doesnt necessarily mean things are constantly changing in the long run, Stroud said. Now we know that even if animals appear to be staying the same, evolution is still happening.

For more on this research, see Paradox of Stasis Lizard Study Challenges the Rules of Evolutionary Biology.

Reference: Fluctuating selection maintains distinct species phenotypes in an ecological community in the wild by James T. Stroud, Michael P. Moore, R. Brian Langerhans and Jonathan B. Losos, 9 October 2023,Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2222071120

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Natural Selection Surprises: Evolutionary Lessons From the Wild Lizards of Florida - SciTechDaily

Biology

Hybrid Transistors with Silk Protein Set the Stage for Integration of … – Tufts Now

Your phone may have more than 15 billion tiny transistors packed into its microprocessor chips. The transistors are made of silicon, metals like gold and copper, and insulators that together take an electric current and convert it to 1s and 0s to communicate information and store it. The transistor materials are inorganic, basically derived from rock and metal.

But what if you could make these fundamental electronic components part biological, able to respond directly to the environment and change like living tissue?

This is what a team at Tufts University Silklab did when they created transistors replacing the insulating material with biological silk. They reported their findings in Advanced Materials.

Silk fibrointhe structural protein of silk fiberscan be precisely deposited onto surfaces and easily modified with other chemical and biological molecules to change its properties. Silk functionalized in this manner can pick up and detect a wide range of components from the body or environment.

The teams first demonstration of a prototype device used the hybrid transistors with silk fibroin to make a highly sensitive and ultrafast breath sensor, detecting changes in humidity. Further modifications of the silk layer in the transistors could enable devices to detect some cardiovascular and pulmonary diseases, as well as sleep apnea, or pick up carbon dioxide levels and other gases and molecules in the breath that might provide diagnostic information. Used with blood plasma, they could potentially provide information on levels of oxygenation and glucose, circulating antibodies, and more.

Prior to the development of the hybrid transistors, the Silklab, led by Fiorenzo Omenetto, the Frank C. Doble Professor of engineering, had already used fibroin to make bioactive inks for fabrics that can detect changes in the environment or on the body, sensing tattoos that can be placed under the skin or on the teeth to monitor health and diet, and sensors that can be printed on any surface to detect pathogens like the virus responsible for COVID-19.

A transistor is simply an electrical switch, with a metal electrical lead coming in and another going out. In between the leads is the semiconductor material, so-called because its not able to conduct electricity unless coaxed.

Another source of electrical input called a gate is separated from everything else by an insulator. The gate acts as the key to turn the transistor on and off. It triggers the on-state when a threshold voltage creates an electric field across the insulator, priming electron movement in the semiconductor and starting the flow of current through the leads.

In a biological hybrid transistor, a silk layer is used as the insulator, and when it absorbs moisture, it acts like a gel carrying whatever ions (electrically charged molecules) are contained within. The gate triggers the on-state by rearranging ions in the silk gel. By changing the ionic composition in the silk, the transistor operation changes, allowing it to be triggered by any gate value between zero and one.

You could imagine creating circuits that make use of information that is not represented by the discrete binary levels used in digital computing, but can process variable information as in analog computing, with the variation caused by changing whats inside the silk insulator, said Omenetto. This opens up the possibility of introducing biology into computing within modern microprocessors. Of course, the most powerful known biological computer is the brain, which processes information with variable levels of chemical and electrical signals.

The technical challenge in creating hybrid biological transistors was to achieve silk processing at the nanoscale, down to 10nm or less than 1/10,000th the diameter of a human hair. Having achieved that, we can now make hybrid transistors with the same fabrication processes that are used for commercial chip manufacturing, said Beom Joon Kim, postdoctoral researcher at the School of Engineering. This means you can make a billion of these with capabilities available today.

Having billions of transistor nodes with connections reconfigured by biological processes in the silk could lead to microprocessors that could act like the neural networks used in AI. Looking ahead, one could imagine having integrated circuits that train themselves, respond to environmental signals, and record memory directly in the transistors rather than sending it to separate storage, said Omenetto.

Devices detecting and responding to more complex biological states, as well as large-scale analog and neuromorphic computing are yet to be created. Omenetto is optimistic about future opportunities. This opens up a new way of thinking about the interface between electronics and biology, with many important fundamental discoveries and applications ahead.

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Hybrid Transistors with Silk Protein Set the Stage for Integration of ... - Tufts Now

Biology

NASA ROSES-23 Amendment 54: E.9-E.11 Space Biology … – Astrobiology News

View of tomatoes growing in the eXposed Root On-Orbit Test System (XROOTS) facility. NASA ID: iss068e018681 iss068e018681 (Oct. 25, 2022) larger image

The Space Biology Program solicits and funds research that will increase NASAs understanding of how living systems respond to the unique environments that are encountered during space exploration, including the Low Earth Orbit (LEO) environment inside the International Space Station (ISS) and deep space conditions beyond LEO, including transit to and maintenance in Lunar and Martian environments.

More information about the Space Biology Program can be found at: https://science.nasa.gov/biological-physical/programs/space-biology.

ROSES-2023 Amendment 54 Announces that:

1) E.9 Space Biology: Plant Studies and E.10 Space Biology: Animal Studies are being deferred to ROSES-2024, to be released February 14, 2024. 2) E.11 Research Pathfinder for Beyond Low Earth Orbit Space Biology Investigations will not be solicited in ROSES-2023, nor does NASA anticipate soliciting it in ROSES-2024.

On or about October 12, 2023, this Amendment to the NASA Research Announcement Research Opportunities in Space and Earth Sciences (ROSES) 2023 (NNH23ZDA001N) will be posted on the NASA research opportunity homepage at https://solicitation.nasaprs.com/ROSES2023 and will appear on SARAs ROSES blog at: https://science.nasa.gov/researchers/sara/grant-solicitations/roses-2023/

Questions concerning any of these space biology programs may be directed to Sharmila Bhattacharya at spacebiology@nasaprs.com.

Astrobiology

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NASA ROSES-23 Amendment 54: E.9-E.11 Space Biology ... - Astrobiology News