Xenobots, tiny living machines, can duplicate themselves.
Strange and complex behavior of frog cell blobs
A xenobot “parent,” shaped like a hungry Pac-Man (shown in red false color), created an “offspring” xenobot (green sphere) by gathering loose frog cells in its opening.
Tiny “living machines” made of frog cells can make copies of themselves. This newly discovered renewal mechanism may help create self-renewing biological machines.
According to Kirstin Petersen, an electrical and computer engineer at Cornell University who studies groups of robots, “this is an extremely exciting breakthrough.” She says self-replicating robots are a big step toward human-free systems.
Researchers described the behavior of xenobots earlier this year (SN: 3/31/21). Small clumps of skin stem cells from frog embryos knitted themselves into small spheres and started moving. Cilia, or cellular extensions, powered the xenobots around their lab dishes.
The findings are published in the Proceedings of the National Academy of Sciences on Dec. 7. The xenobots can gather loose frog cells into spheres, which then form xenobots.
The researchers call this type of movement-induced reproduction kinematic self-replication. The study's coauthor, Douglas Blackiston of Tufts University in Medford, Massachusetts, and Harvard University, says this is typical. For example, sexual reproduction requires parental sperm and egg cells. Sometimes cells split or budded off from a parent.
“This is unique,” Blackiston says. These xenobots “find loose parts in the environment and cobble them together.” This second generation of xenobots can move like their parents, Blackiston says.
The researchers discovered that spheroid xenobots could only produce one more generation before dying out. The original xenobots' shape was predicted by an artificial intelligence program, allowing for four generations of replication.
A C shape, like an openmouthed Pac-Man, was predicted to be a more efficient progenitor. When improved xenobots were let loose in a dish, they began scooping up loose cells into their gaping “mouths,” forming more sphere-shaped bots (see image below). As many as 50 cells clumped together in the opening of a parent to form a mobile offspring. A xenobot is made up of 4,000–6,000 frog cells.
Petersen likes the Xenobots' small size. “The fact that they were able to do this at such a small scale just makes it even better,” she says. Miniature xenobots could sculpt tissues for implantation or deliver therapeutics inside the body.
Beyond the xenobots' potential jobs, the research advances an important science, says study coauthor and Tufts developmental biologist Michael Levin. The science of anticipating and controlling the outcomes of complex systems, he says.
“No one could have predicted this,” Levin says. “They regularly surprise us.” Researchers can use xenobots to test the unexpected. “This is about advancing the science of being less surprised,” Levin says.
More on Science
Bob Service
3 years ago
Did volcanic 'glasses' play a role in igniting early life?
Quenched lava may have aided in the formation of long RNA strands required by primitive life.
It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.
Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.
The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.
Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.
However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.
Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.
He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."
Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.
The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.
Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."
Michael Hunter, MD
2 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
Sara_Mednick
3 years ago
Since I'm a scientist, I oppose biohacking
Understanding your own energy depletion and restoration is how to truly optimize
Hack has meant many bad things for centuries. In the 1800s, a hack was a meager horse used to transport goods.
Modern usage describes a butcher or ax murderer's cleaver chop. The 1980s programming boom distinguished elegant code from "hacks". Both got you to your goal, but the latter made any programmer cringe and mutter about changing the code. From this emerged the hacker trope, the friendless anti-villain living in a murky hovel lit by the computer monitor, eating junk food and breaking into databases to highlight security system failures or steal hotdog money.
Now, start-a-billion-dollar-business-from-your-garage types have shifted their sights from app development to DIY biology, coining the term "bio-hack". This is a required keyword and meta tag for every fitness-related podcast, book, conference, app, or device.
Bio-hacking involves bypassing your body and mind's security systems to achieve a goal. Many biohackers' initial goals were reasonable, like lowering blood pressure and weight. Encouraged by their own progress, self-determination, and seemingly exquisite control of their biology, they aimed to outsmart aging and death to live 180 to 1000 years (summarized well in this vox.com article).
With this grandiose north star, the hunt for novel supplements and genetic engineering began.
Companies selling do-it-yourself biological manipulations cite lab studies in mice as proof of their safety and success in reversing age-related diseases or promoting longevity in humans (the goal changes depending on whether a company is talking to the federal government or private donors).
The FDA is slower than science, they say. Why not alter your biochemistry by buying pills online, editing your DNA with a CRISPR kit, or using a sauna delivered to your home? How about a microchip or electrical stimulator?
What could go wrong?
I'm not the neo-police, making citizen's arrests every time someone introduces a new plumbing gadget or extrapolates from animal research on resveratrol or catechins that we should drink more red wine or eat more chocolate. As a scientist who's spent her career asking, "Can we get better?" I've come to view bio-hacking as misguided, profit-driven, and counterproductive to its followers' goals.
We're creatures of nature. Despite all the new gadgets and bio-hacks, we still use Roman plumbing technology, and the best way to stay fit, sharp, and happy is to follow a recipe passed down since the beginning of time. Bacteria, plants, and all natural beings are rhythmic, with alternating periods of high activity and dormancy, whether measured in seconds, hours, days, or seasons. Nature repeats successful patterns.
During the Upstate, every cell in your body is naturally primed and pumped full of glycogen and ATP (your cells' energy currencies), as well as cortisol, which supports your muscles, heart, metabolism, cognitive prowess, emotional regulation, and general "get 'er done" attitude. This big energy release depletes your batteries and requires the Downstate, when your subsystems recharge at the cellular level.
Downstates are when you give your heart a break from pumping nutrient-rich blood through your body; when you give your metabolism a break from inflammation, oxidative stress, and sympathetic arousal caused by eating fast food — or just eating too fast; or when you give your mind a chance to wander, think bigger thoughts, and come up with new creative solutions. When you're responding to notifications, emails, and fires, you can't relax.
Downstates aren't just for consistently recharging your battery. By spending time in the Downstate, your body and brain get extra energy and nutrients, allowing you to grow smarter, faster, stronger, and more self-regulated. This state supports half-marathon training, exam prep, and mediation. As we age, spending more time in the Downstate is key to mental and physical health, well-being, and longevity.
When you prioritize energy-demanding activities during Upstate periods and energy-replenishing activities during Downstate periods, all your subsystems, including cardiovascular, metabolic, muscular, cognitive, and emotional, hum along at their optimal settings. When you synchronize the Upstates and Downstates of these individual rhythms, their functioning improves. A hard workout causes autonomic stress, which triggers Downstate recovery.
By choosing the right timing and type of exercise during the day, you can ensure a deeper recovery and greater readiness for the next workout by working with your natural rhythms and strengthening your autonomic and sleep Downstates.
Morning cardio workouts increase deep sleep compared to afternoon workouts. Timing and type of meals determine when your sleep hormone melatonin is released, ushering in sleep.
Rhythm isn't a hack. It's not a way to cheat the system or the boss. Nature has honed its optimization wisdom over trillions of days and nights. Stop looking for quick fixes. You're a whole system made of smaller subsystems that must work together to function well. No one pill or subsystem will make it all work. Understanding and coordinating your rhythms is free, easy, and only benefits you.
Dr. Sara C. Mednick is a cognitive neuroscientist at UC Irvine and author of The Power of the Downstate (HachetteGO)
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Saskia Ketz
2 years ago
I hate marketing for my business, but here's how I push myself to keep going
Start now.
When it comes to building my business, I’m passionate about a lot of things. I love creating user experiences that simplify branding essentials. I love creating new typefaces and color combinations to inspire logo designers. I love fixing problems to improve my product.
Business marketing isn't my thing.
This is shared by many. Many solopreneurs, like me, struggle to advertise their business and drive themselves to work on it.
Without a lot of promotion, no company will succeed. Marketing is 80% of developing a firm, and when you're starting out, it's even more. Some believe that you shouldn't build anything until you've begun marketing your idea and found enough buyers.
Marketing your business without marketing experience is difficult. There are various outlets and techniques to learn. Instead of figuring out where to start, it's easier to return to your area of expertise, whether that's writing, designing product features, or improving your site's back end. Right?
First, realize that your role as a founder is to market your firm. Being a founder focused on product, I rarely work on it.
Secondly, use these basic methods that have helped me dedicate adequate time and focus to marketing. They're all simple to apply, and they've increased my business's visibility and success.
1. Establish buckets for every task.
You've probably heard to schedule tasks you don't like. As simple as it sounds, blocking a substantial piece of my workday for marketing duties like LinkedIn or Twitter outreach, AppSumo customer support, or SEO has forced me to spend time on them.
Giving me lots of room to focus on product development has helped even more. Sure, this means scheduling time to work on product enhancements after my four-hour marketing sprint.
It also involves making space to store product inspiration and ideas throughout the day so I don't get distracted. This is like the advice to keep a notebook beside your bed to write down your insomniac ideas. I keep fonts, color palettes, and product ideas in folders on my desktop. Knowing these concepts won't be lost lets me focus on marketing in the moment. When I have limited time to work on something, I don't have to conduct the research I've been collecting, so I can get more done faster.
2. Look for various accountability systems
Accountability is essential for self-discipline. To keep focused on my marketing tasks, I've needed various streams of accountability, big and little.
Accountability groups are great for bigger things. SaaS Camp, a sales outreach coaching program, is mine. We discuss marketing duties and results every week. This motivates me to do enough each week to be proud of my accomplishments. Yet hearing what works (or doesn't) for others gives me benchmarks for my own marketing outcomes and plenty of fresh techniques to attempt.
… say, I want to DM 50 people on Twitter about my product — I get that many Q-tips and place them in one pen holder on my desk.
The best accountability group can't watch you 24/7. I use a friend's simple method that shouldn't work (but it does). When I have a lot of marketing chores, like DMing 50 Twitter users about my product, That many Q-tips go in my desk pen holder. After each task, I relocate one Q-tip to an empty pen holder. When you have a lot of minor jobs to perform, it helps to see your progress. You might use toothpicks, M&Ms, or anything else you have a lot of.
3. Continue to monitor your feedback loops
Knowing which marketing methods work best requires monitoring results. As an entrepreneur with little go-to-market expertise, every tactic I pursue is an experiment. I need to know how each trial is doing to maximize my time.
I placed Google and Facebook advertisements on hold since they took too much time and money to obtain Return. LinkedIn outreach has been invaluable to me. I feel that talking to potential consumers one-on-one is the fastest method to grasp their problem areas, figure out my messaging, and find product market fit.
Data proximity offers another benefit. Seeing positive results makes it simpler to maintain doing a work you don't like. Why every fitness program tracks progress.
Marketing's goal is to increase customers and revenues, therefore I've found it helpful to track those metrics and celebrate monthly advances. I provide these updates for extra accountability.
Finding faster feedback loops is also motivating. Marketing brings more clients and feedback, in my opinion. Product-focused founders love that feedback. Positive reviews make me proud that my product is benefitting others, while negative ones provide me with suggestions for product changes that can improve my business.
The best advice I can give a lone creator who's afraid of marketing is to just start. Start early to learn by doing and reduce marketing stress. Start early to develop habits and successes that will keep you going. The sooner you start, the sooner you'll have enough consumers to return to your favorite work.
Sammy Abdullah
2 years ago
Payouts to founders at IPO
How much do startup founders make after an IPO? We looked at 2018's major tech IPOs. Paydays aren't what founders took home at the IPO (shares are normally locked up for 6 months), but what they were worth at the IPO price on the day the firm went public. It's not cash, but it's nice. Here's the data.
Several points are noteworthy.
Huge payoffs. Median and average pay were $399m and $918m. Average and median homeownership were 9% and 12%.
Coinbase, Uber, UI Path. Uber, Zoom, Spotify, UI Path, and Coinbase founders raised billions. Zoom's founder owned 19% and Spotify's 28% and 13%. Brian Armstrong controlled 20% of Coinbase at IPO and was worth $15bn. Preserving as much equity as possible by staying cash-efficient or raising at high valuations also helps.
The smallest was Ping. Ping's compensation was the smallest. Andre Duand owned 2% but was worth $20m at IPO. That's less than some billion-dollar paydays, but still good.
IPOs can be lucrative, as you can see. Preserving equity could be the difference between a $20mm and $15bln payday (Coinbase).
Jari Roomer
3 years ago
Successful people have this one skill.
Without self-control, you'll waste time chasing dopamine fixes.
I found a powerful quote in Tony Robbins' Awaken The Giant Within:
“Most of the challenges that we have in our personal lives come from a short-term focus” — Tony Robbins
Most people are short-term oriented, but highly successful people are long-term oriented.
Successful people act in line with their long-term goals and values, while the rest are distracted by short-term pleasures and dopamine fixes.
Instant gratification wrecks lives
Instant pleasure is fleeting. Quickly fading effects leave you craving more stimulation.
Before you know it, you're in a cycle of quick fixes. This explains binging on food, social media, and Netflix.
These things cause a dopamine spike, which is entertaining. This dopamine spike crashes quickly, leaving you craving more stimulation.
It's fine to watch TV or play video games occasionally. Problems arise when brain impulses aren't controlled. You waste hours chasing dopamine fixes.
Instant gratification becomes problematic when it interferes with long-term goals, happiness, and life fulfillment.
Most rewarding things require delay
Life's greatest rewards require patience and delayed gratification. They must be earned through patience, consistency, and effort.
Ex:
A fit, healthy body
A deep connection with your spouse
A thriving career/business
A healthy financial situation
These are some of life's most rewarding things, but they take work and patience. They all require the ability to delay gratification.
To have a healthy bank account, you must save (and invest) a large portion of your monthly income. This means no new tech or clothes.
If you want a fit, healthy body, you must eat better and exercise three times a week. So no fast food and Netflix.
It's a battle between what you want now and what you want most.
Successful people choose what they want most over what they want now. It's a major difference.
Instant vs. delayed gratification
Most people subconsciously prefer instant rewards over future rewards, even if the future rewards are more significant.
We humans aren't logical. Emotions and instincts drive us. So we act against our goals and values.
Fortunately, instant gratification bias can be overridden. This is a modern superpower. Effective methods include:
#1: Train your brain to handle overstimulation
Training your brain to function without constant stimulation is a powerful change. Boredom can lead to long-term rewards.
Unlike impulsive shopping, saving money is boring. Having lots of cash is amazing.
Compared to video games, deep work is boring. A successful online business is rewarding.
Reading books is boring compared to scrolling through funny videos on social media. Knowledge is invaluable.
You can't do these things if your brain is overstimulated. Your impulses will control you. To reduce overstimulation addiction, try:
Daily meditation (10 minutes is enough)
Daily study/work for 90 minutes (no distractions allowed)
First hour of the day without phone, social media, and Netflix
Nature walks, journaling, reading, sports, etc.
#2: Make Important Activities Less Intimidating
Instant gratification helps us cope with stress. Starting a book or business can be intimidating. Video games and social media offer a quick escape in such situations.
Make intimidating tasks less so. Break them down into small tasks. Start a new business/side-hustle by:
Get domain name
Design website
Write out a business plan
Research competition/peers
Approach first potential client
Instead of one big mountain, divide it into smaller sub-tasks. This makes a task easier and less intimidating.
#3: Plan ahead for important activities
Distractions will invade unplanned time. Your time is dictated by your impulses, which are usually Netflix, social media, fast food, and video games. It wants quick rewards and dopamine fixes.
Plan your days and be proactive with your time. Studies show that scheduling activities makes you 3x more likely to do them.
To achieve big goals, you must plan. Don't gamble.
Want to get fit? Schedule next week's workouts. Want a side-job? Schedule your work time.