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CatLady78

Profile Information

Gender: Female
Current location: India
Member since: Thu Jun 18, 2020, 11:40 AM
Number of posts: 497

About Me

I am an old-timer. I posted here as nam78_two for 4-5 years (2004 or 5 to 2009-10) in the Bush, Obama years.

Journal Archives

I am with you - she was a product of her times

If she were alive today she would have progressed in her views (unlike those who attack her from the right). In her time, there was widespread support for eugenics-a huge error but the irony is that those who fake outrage over it from the right (think Fox News, the GOP etc) still think like that today. We have to learn to separate people who were imperfect or made errors from the irredeemably regressive.
Unlike many of those who attack her, she actually did a lot of good.

That said, PP is doing the right thing strategically for the simple reason that they face many attacks as is. Their work is very important-anything that lets the actual racists and sexists from the right smear them more easily is best dispensed with. Fortunately a lot of these smears also come from incredibly stupid people like James O'Keefe.

Personalized Microbots Can Deliver Drugs to Mammalian Cells

That is neat...hybrid microbots for drug delivery..

https://publishing.aip.org/publications/latest-content/personalized-microrobots-swim-through-biological-barriers-deliver-drugs-to-cells/


Personalized Microrobots Swim Through Biological Barriers, Deliver Drugs to Cells


Illustration (top) and scanning electron microscopy image (bottom) of biohybrid bacterial microswimmers, which were fabricated by combining genetically engineered E. coli MG1655 and nanoerythrosomes made from red blood cells. A biotin-streptavidin interaction was used to attach nanoerythrosomes to the bacterial membrane. CREDIT:Image courtesy of the authors

WASHINGTON, April 7, 2020 — Tiny biohybrid robots on the micrometer scale can swim through the body and deliver drugs to tumors or provide other cargo-carrying functions. The natural environmental sensing tendencies of bacteria mean they can navigate toward certain chemicals or be remotely controlled using magnetic or sound signals.

To be successful, these tiny biological robots must consist of materials that can pass clearance through the body’s immune response. They also have to be able to swim quickly through viscous environments and penetrate tissue cells to deliver cargo.

In a paper published this week in APL Bioengineering, from AIP Publishing, researchers fabricated biohybrid bacterial microswimmers by combining a genetically engineered E. coli MG1655 substrain and nanoerythrosomes, small structures made from red blood cells.

Nanoerythrosomes are nanovesicles derived from red blood cells by emptying the cells, keeping the membranes and filtering them down to nanoscale size. These tiny red blood cell carriers attach to the bacterial membrane using the powerful noncovalent biological bond between biotin and streptavidin. This process preserves two important red blood cell membrane proteins: TER119 needed to attach the nanoerythrosomes, and CD47 to prevent macrophage uptake.

The E. coli MG 1655 serves as a bioactuator performing the mechanical work of propelling through the body as a molecular engine using flagellar rotation. The swimming capabilities of the bacteria were assessed using a custom-built 2D object-tracking algorithm and 20 videos taken as raw data to document their performance.

Biohybrid microswimmers with bacteria carrying red blood cell nanoerythrosomes performed at speeds 40% faster than other E. coli-powered microparticles-based biohybrid microswimmers, and the work demonstrated a reduced immune response due to the nanoscale size of the nanoerythrosomes and adjustments to the density of coverage of nanoerythrosomes on the bacterial membrane.

These biohybrid swimmers could deliver drugs faster, due to their swimming speed, and encounter less immune response, due to their composition. The researchers plan to continue their work to further tune the immune clearance of the microrobots and investigate how they might penetrate cells and release their cargo in the tumor microenvironment.
“This work is an important stepping stone in our overarching goal of developing and deploying biohybrid microrobots for therapeutic cargo delivery,” author Metin Sitti said. “If you decrease the size of red blood cells to nanoscale and functionalize the body of the bacteria, you could obtain additional superior properties that will be crucial in the translation of the medical microrobotics to clinics.”


Edit: I edited the title in the interests of truth in advertising . This article has nothing whatsoever to do with the delivery of drugs to prison cells!


Buffet has been investing in fracking?

Did not know that. Thanks for the article..

Lissencephaly-1 Protein Regulates the Molecular Motor Dynein

There are 3 major classes of cytoskeletal molecular motors (as far as I know): myosin, kinesin and dynein. This article is about the regulation of dynein by a protein associated with Lissencephaly (a brain disorder). Apparently Lis-1 which was previously considered an inhibitor of dynein function is actually an activator.

https://phys.org/news/2020-04-biochemists-unveil-molecular-mechanism-motor.html
Excerpts below:


The lissencephaly-1, or Lis1 protein, activates the dynein motor so it can transport cellular cargo. The dynein switches between "off" (left) and "on" (right). Lis1 binds to dynein when it is on, preventing the dynein from switching to an "off" state. Credit: Markus Lab/Colorado State University

Movement signals life, and nowhere is this truer than inside a living cell. The millions of proteins and molecules within each of our cells bend, travel and conform in a complex but orchestrated pattern, regulated by the genes that encode what goes where and when. As part of that pattern, an important class of proteins called dynein transport and deliver various cellular cargoes between different areas of the cell.

Colorado State University biochemistry researcher Steven Markus is particularly intrigued by these large, intracellular motor proteins that move methodically along a network of filamentous tracks called microtubules.

How important is dynein? If dynein were to disappear, we wouldn't live past a few mitotic cellular divisions. And many neurological diseases, including one called lissencephaly, are linked to defects in dynein function. The goal of many labs, including Markus', is to understand why.

His research team has made a leap in that understanding by unveiling, in intricate detail, the mechanism by which one particular molecule affects dynein function. While it was long known that the lissencephaly-1 gene, or Lis1, affects dynein activity, the details were unclear. Markus and his team have revealed exactly how Lis1 activates dynein by preventing dynein's ability to turn itself off, stabilizing it in an "open," uninhibited conformation.

The new finding flies in the face of previously accepted views that Lis1 acted as an inhibitor of dynein. According to the Markus lab's new study, published April 27 in Nature Cell Biology, the exact opposite is true: Lis1 activates dynein, working to wedge itself in such a way that the motor protein is prevented from folding itself into an "off" state—inhibiting its ability to auto-inhibit, the researchers explain.


The researchers used a combination of cutting-edge techniques to draw their conclusions, including high-resolution electron microscopy. They used this to visualize the dynein motor in its "off" (left) and "on" (right) states. Credit: Markus Lab/Colorado State University

Understanding molecular basis of disease

A person with lissencephaly, or "smooth brain," suffers seizures and limited motor function and rarely lives past a few years of age. This devastating disease is associated with a mutation in Lis1, a gene that encodes a critical regulator of dynein.

"I'm interested in the molecular basis for these diseases," said Markus, assistant professor in the Department of Biochemistry and Molecular Biology. "There will be no therapeutic interventions without understanding how these molecules function." Beyond that, Markus says, "molecular motors are fun, because we can purify these motors and watch them walk on microtubules in real time using fluorescence microscopy"—which is exactly what the team did for their study.

To carry out their experiments, the researchers employed budding yeast cells as a model system.

The researchers employed several techniques to make their conclusions. The most important was real-time single-molecule imaging. Using a high-yield technique they developed in the lab, the team purified dynein, added a fluorescent molecule, and assembled microscope imaging chambers with purified microtubules to watch the dynein "zip along," Markus said. This technique allowed them to establish the role of the auto-inhibited conformation in dynein motility.

They also used electron microscopy to take very high-resolution still pictures to determine if the dynein molecules indeed adopted an auto-inhibited conformation, which was unclear when they began their study.

Markus plans to conduct other experiments, using the same yeast cells, to further probe the role of Lis1 in what he and colleagues think is a multi-step pathway that activates dynein. He also hopes to work with neuroscientists at CSU to determine whether the Lis1 activation mechanism functions similarly in neurons. There, the goal will be to provide even further knowledge into how brain diseases like lissencephaly occur at the molecular level.


Edit: I updated this to read cytoskeletal motor proteins. I was forgetting about other motors like the F0F1-ATP Synthase (about which I know nothing). These are the motor molecules that use the actin- and microtubule-based cytoskeleton as their tracks.

Cellular Nanosponge Decoys For SARS-CoV-2

I usually have two rules for any posts I make in this forum - 1) nothing too close to home (i.e. research from scientists or labs known to me) and 2) nothing tied to a specific company, product, therapy etc.
I am making an exception for this, though it is the latter, as it is both topical and interesting:


https://medicalxpress.com/news/2020-07-cell-like-decoys-mop-viruses-humans.html



In this illustration, six decoys surround a SARS-CoV-2 virus particle before it can reach a human cell. Credit: David Baillot, UC San Diego Jacobs School of Engineering, CC BY-ND


July 9, 2020 by Liangfang Zhang, The Conversation

Researchers around the world are working frantically to develop COVID-19 vaccines meant to target and attack the SARS-CoV-2 virus. Researchers in my nanoengineering lab are taking a different approach toward stopping SARS-CoV-2. Instead of playing offense and stimulating the immune system to attack the SARS-CoV-2 virus, we're playing defense. We're working to shield the healthy human cells the virus invades.

Conceptually, the strategy is simple. We create decoys that look like the human cells the SARS-CoV-2 virus invades. So far, we've made lung-cell decoys and immune-cell decoys. These cell decoys attract and neutralize the SARS-CoV-2 virus, leaving the real lung or immune cells healthy.

To make the decoys, we collect the outer membranes of the lung or immune cells and wrap them around a core made of biodegradable nanoparticles. From the outside the decoys look the same as the human cells they are impersonating. Our decoys are hundreds of times smaller in diameter than an actual lung or immune cell, but they have all the same cellular hardware sticking out of them.

We call them "nanosponges" because they soak up harmful pathogens and toxins that attack the cells they impersonate.

Why it matters

Vaccines are critical for protecting against viral infections, but as viruses mutate they can render vaccines and treatments ineffective. This is why new flu vaccines are developed each year. Fortunately, SARS-CoV-2 doesn't appear to mutate as quickly as influenza viruses, but this highlights the need for alternatives that are unaffected by mutations.

Cellular nanosponges are a new kind of drug. We made the first nanosponges using human red blood cell membranes, and these are the furthest along in the regulatory process, having undergone all stages of pre-clinical testing.

There is also the possibility that our immune-cell nanosponges could soak up the inflammatory cytokine proteins that are triggering the dangerous immune system overreactions in some people suffering from COVID-19.


Nanodevices Track Cell Changes Over Time

More cool work at the interface of physics and biology. These scientists used silicon-based devices to track intracellular forces in developing mouse embryoes.


At this point in development, the embryo chromosomes (which appear red in the centre) are preparing to separate during the first cell division. The device prongs can be seen fluorescing green, with green-fluorescing actin around the periphery. Credit: Professor Tony Perry


https://phys.org/news/2020-05-nanodevices-cells-tracking.html
https://www.nature.com/articles/s41563-020-0685-9
Excerpts below:


Nanodevices show how cells change with time, by tracking from the inside

For the first time, scientists have introduced minuscule tracking devices directly into the interior of mammalian cells, giving an unprecedented peek into the processes that govern the beginning of development.

This work on one-cell embryos is set to shift our understanding of the mechanisms that underpin cellular behaviour in general, and may ultimately provide insights into what goes wrong in ageing and disease.

The research, led by Professor Tony Perry from the Department of Biology and Biochemistry at the University of Bath, involved injecting a silicon-based nanodevice together with sperm into the egg cell of a mouse. The result was a healthy, fertilised egg containing a tracking device.

The tiny devices are a little like spiders, complete with eight highly flexible 'legs'. The legs measure the 'pulling and pushing' forces exerted in the cell interior to a very high level of precision, thereby revealing the cellular forces at play and showing how intracellular matter rearranged itself over time.

The nanodevices are incredibly thin—similar to some of the cell's structural components, and measuring 22 nanometres, making them approximately 100,000 times thinner than a pound coin. This means they have the flexibility to register the movement of the cell's cytoplasm as the one-cell embryo embarks on its voyage towards becoming a two-cell embryo.

"This is the first glimpse of the physics of any cell on this scale from within," said Professor Perry. "It's the first time anyone has seen from the inside how cell material moves around and organises itself."

"From studies in biology and embryology, we know about certain molecules and cellular phenomena, and we have woven this information into a reductionist narrative of how things work, but now this narrative is changing," said Professor Perry. The narrative was written largely by biologists, who brought with them the questions and tools of biology. What was missing was physics. Physics asks about the forces driving a cell's behaviour, and provides a top-down approach to finding the answer.

"We can now look at the cell as a whole, not just the nuts and bolts that make it."

Mouse embryos were chosen for the study because of their relatively large size (they measure 100 microns, or 100-millionths of a metre, in diameter, compared to a regular cell which is only 10 microns [10-millionths of a metre] in diameter). This meant that inside each embryo, there was space for a tracking device.

The researchers made their measurements by examining video recordings taken through a microscope as the embryo developed. "Sometimes the devices were pitched and twisted by forces that were even greater than those inside muscle cells," said Professor Perry. "At other times, the devices moved very little, showing the cell interior had become calm. There was nothing random about these processes—from the moment you have a one-cell embryo, everything is done in a predictable way. The physics is programmed."


From the abstract:
The nanodevices reported reduced cytoplasmic mechanical activity during chromosome alignment and indicated that cytoplasmic stiffening occurred during embryo elongation, followed by rapid cytoplasmic softening during cytokinesis (cell division).

Everything you said on this thread


I am childfree for many of these reasons.

Hah

I have disliked all forms of religion for as long as I can remember.....probably because it was never forced on me. Having no real religious indoctrination, as a child I immediately perceived a conflict between religion and science (which I liked).



Rotation Plays a Role in Jamming-Unjamming Transition in Cells

Interesting work at the interface between physics and biology.


Spinning around: scanning electron microscope image of C. reinhardtii cells (Courtesy: Dartmouth Electron Microscope Facility, Dartmouth College)


https://physicsworld.com/a/active-rotation-plays-a-role-in-the-jamming-unjamming-transition-in-living-cells/


Active rotation plays a role in the jamming–unjamming transition in living cells

New research offers insight into the role of rotation in the self-assembly of living cells. The work is described in Soft Matter and was done by Linda Ravazzano at the University of Milan under the supervision of Stefano Zapperi and in collaboration with Caterina La Porta’s research group.

Computer simulations and experiments with algae provided the team with information about the jamming and unjamming of cells at high densities. This research could lead to a better understanding of the differences between healthy and cancerous cells in human tissue.

The self-assembly of cells into tissues sits firmly at the interface of physics and biology. Cells are complex biological systems that sense changes in their environment and communicate with other cells, but they can also exhibit self-organization that is driven purely by thermodynamics.

Active torque and jamming
The jamming transition occurs when, without crystallizing, a system of particles becomes so closely packed that it behaves as a solid. This phenomenon, which has been observed in living cells, generally occurs when the density of the system is increased.

C. reinhardtii cells do not exhibit jamming at high density, because when they become crowded, their motility increases. Ravazzano and colleagues suggest that the active rotation of the algae increases in response to crowding, which opposes jamming.

This hypothesis was tested in simulation by preparing the disks with zero propulsion at the passive jamming volume fraction and increasing the rotation. A transition from a jammed to an unjammed state at a threshold torque was observed. Though more research on the response of the algae is needed, it is evidently possible for active torque to trigger unjamming.

The addition of self-propulsion to the model complicates the self-assembly behaviour. As the torque is increased, the system first jams and then unjams. The explanation offered by the Milan team is that a crossover between propulsion and rotation determines the behaviour of the algae.

At low torques, the self-propelled particles avoid jamming because they move coherently, but the rotation randomizes their motion and they undergo jamming as it is increased. At higher torques, the rotation dominates over self- propulsion and the unjamming transition is observed as before.

The outlook
In their paper describing the study, the researchers highlight the similarities between the jamming transition of the disks and the change from a solid to liquid like state observed in healthy versus cancerous cells. They also remark on the “possible role for rotations in collective cell migration,” and give the observed formation of vortices in confined epithelial cells as an example.



The jamming phenomenon was characterized here in algae and I am assuming the torque described here is generated by their flagella:

https://en.m.wikipedia.org/wiki/Chlamydomonas_reinhardtii

But this is of interest to physicists investigating cell behavior generally and with specific relevance to cancer. Remarkable - instances like those described below where purely theoretical predictions apparently hit the nail on the head.

https://www.wired.com/2016/08/jammed-cells-expose-physics-cancer/


The Mystery of How Cancer Cells Barrel Through Your Body

IN 1995, WHILE he was a graduate student at McGill University in Montreal, the biomedical scientist Peter Friedl saw something so startling it kept him awake for several nights. Coordinated groups of cancer cells he was growing in his adviser’s lab started moving through a network of fibers meant to mimic the spaces between cells in the human body.

Physicists have long provided doctors with tumor-fighting tools such as radiation and proton beams. But only recently has anyone seriously considered the notion that purely physical concepts might help us understand the basic biology of one of the world’s deadliest phenomena. In the past few years, physicists studying metastasis have generated surprisingly precise predictions of cell behavior.

Lisa Manning, a physicist at Syracuse University, read Fredberg’s paper and decided to put his idea into action. She and colleagues used a two-dimensional model of cells that are connected along edges and at vertices, filling all space. The model yielded an order parameter—a measurable number that quantifies a material’s internal order—that they called the “shape index.” The shape index relates the perimeter of a two-dimensional slice of the cell and its total surface area. “We made what I would consider a ridiculously strict prediction: When that number is equal to 3.81 or below, the tissue is a solid, and when that number is above 3.81, that tissue is a fluid,” Manning said. “I asked Jeff Fredberg to go look at this, and he did, and it worked perfectly.”

Fredberg saw that lung cells with a shape index above 3.81 started to mobilize and squeeze past each other. Manning’s prediction “came out of pure theory, pure thought,” he said. “It’s really an astounding validation of a physical theory.”
A program officer with the Physical Sciences in Oncology program at the National Cancer Institute learned about the results and encouraged Fredberg to do a similar analysis using cancer cells. The program has given him funding to look for signatures of jamming in breast-cancer cells.

More speculatively, Käs thinks the idea could also yield new avenues for therapies that are gentler than the shock-and-awe approach clinicians typically use to subdue a tumor. “If you can jam a whole tumor, then you have a benign tumor—that I believe,” he said. “If you find something which basically jams cancer cells efficiently and buys you another 20 years, that might be better than very disruptive chemotherapies.” Yet Käs is quick to clarify that he is not sure how a clinician would induce jamming.


The World's Smallest Motor

This is pretty cool. I posted about some motor proteins earlier this week. Scientists have made a motor with just 16 atoms which measures less than a nm (10^-9 m)-i.e. abot a 100,000 times smaller than the diameter of human hair. It uses thermal and electrical energy. I am not sure what quantum tunneling effects are. Regardless, this is pretty cool.

https://phys.org/news/2020-06-smallest-motor-world.html

Scanning Tunneling Microscopy image (magnification about 50-million) of a PdGa surface with six dumbbell shaped acetylene-rotor molecules in different rotation states. The to-scale atomic structure of stator (blue-red) and the acetylene-rotor (grey-white in the slightly left-tilted vertical orientation) are shown schematically on the right. Credit: Empa

Some excerpts:

A research team from Empa and EPFL has developed a molecular motor which consists of only 16 atoms and rotates reliably in one direction. It could allow energy harvesting at the atomic level. The special feature of the motor is that it moves exactly at the boundary between classical motion and quantum tunneling - and has revealed puzzling phenomena to researchers in the quantum realm.

In principle, a molecular machine functions in a similar way to its counterpart in the macro world: it converts energy into a directed movement. Such molecular motors also exist in nature—for example in the form of myosins. Myosins are motor proteins that play an important role in living organisms in the contraction of muscles and the transport of other molecules between cells.

Energy harvesting on the nanoscale
Like a large-scale motor, the 16-atom motor consists of a stator and a rotor, i.e. a fixed and a moving part. The rotor rotates on the surface of the stator (see picture). It can take up six different positions. "For a motor to actually do useful work, it is essential that the stator allows the rotor to move in only one direction," explains Gröning.

Since the energy that drives the motor can come from a random direction, the motor itself must determine the direction of rotation using a ratcheting scheme. However, the atom motor operates opposite of what happens with a ratchet in the macroscopic world with its asymmetrically serrated gear wheel: While the pawl on a ratchet moves up the flat edge and locks in the direction of the steep edge, the atomic variant requires less energy to move up the steep edge of the gear wheel than it does at the flat edge. The movement in the usual 'blocking direction' is therefore preferred and the movement in 'running direction' much less likely. So the movement is virtually only possible in one direction.

The researchers have implemented this 'reverse' ratchet principle in a minimal variant by using a stator with a basically triangular structure consisting of six palladium and six gallium atoms. The trick here is that this structure is rotationally symmetrical, but not mirror-symmetrical.

As a result, the rotor (a symmetrical acetylene molecule) consisting of only four atoms can rotate continuously, although the clockwise and counterclockwise rotation must be different. "The motor therefore has 99% directional stability, which distinguishes it from other similar molecular motors," says Gröning. In this way, the molecular motor opens up a way for energy harvesting at the atomic level.

Energy from two sources
The tiny motor can be powered by both thermal and electrical energy. The thermal energy provokes that the directional rotary motion of the motor changes into rotations in random directions—at room temperature, for example, the rotor rotates back and forth completely randomly at several million revolutions per second.

In contrast, electrical energy generated by an electron scanning microscope, from the tip of which a small current flows into the motors, can cause directional rotations. The energy of a single electron is sufficient to make the rotors continue to rotate by just a sixth of a revolution. The higher the amount of energy supplied, the higher the frequency of movement—but at the same time, the more likely the rotor is to move in a random direction, since too much energy can overcome the pawl in the "wrong" direction.

Back to our mini-motor: It is usually assumed that no friction is generated during tunneling. At the same time, however, no energy is supplied to the system. So how can it be that the rotor always turns in the same direction? The second law of thermodynamics does not allow any exceptions—the only explanation is that there is a loss of energy during tunneling, even if it is extremely small. Gröning and his team have therefore not only developed a toy for molecular craftsmen. "The motor could enable us to study the processes and reasons for energy dissipation in quantum tunneling processes," says the Empa researcher.


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