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CatLady78

Profile Information

Gender: Female
Current location: India
Member since: Thu Jun 18, 2020, 11:40 AM
Number of posts: 479

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

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.


He gets a big pay-out for putting disinfo out.nt

Virus Halts Movement of Mitochondria by Causing Shedding of Motor Proteins

This is an old article but cool...Not sure if there are any updates - I did not see any on pubmed in a brief search. The part about the virus hijacking the motor proteins to propagate itself is speculative if I read that right. Excerpts below.
https://www.futurity.org/to-hijack-neuron-virus-halts-cell-%e2%80%98power-plant%e2%80%99/



In a healthy neuron (left), mitochondria are carried along by motor proteins dynein and kinesin-1. Viral infection (right) floods the cell with calcium (Ca2+), which, when detected by the mitochondrial protein Miro, brings mitochondria to a halt and causes them to shed motor proteins. (Credit: Tal Kramer)

PRINCETON (US) — Viruses that attack the nervous system may thrive by disrupting cell function in order to hijack a neuron’s internal transportation network and spread to other cells.

In a healthy neuron (left), mitochondria are carried along by motor proteins dynein and kinesin-1. Viral infection (right) floods the cell with calcium (Ca2+), which, when detected by the mitochondrial protein Miro, brings mitochondria to a halt and causes them to shed motor proteins. (Credit: Tal Kramer)
[sources]

The team reports in the journal Cell Host and Microbe that viral infection elevates neuron activity, as well as the cell’s level of calcium—a key chemical in cell communication—and brings mitochondrial motion to a halt in the cell’s axon, which connects to and allows communication with other neurons.

The authors propose that the viruses then commandeer the proteins that mitochondria typically use to move about the cell. The pathogens can then freely travel and reproduce within the infected neuron and more easily spread to uninfected cells. When the researchers made the mitochondria less sensitive to calcium the viruses could not spread as quickly or easily.

"And the fact that alpha-herpes infection damages the same key cellular function as neurodegenerative disorders also is striking,” he says. “Understanding how viral infection damages neurons might give us insight into how diseases like Alzheimer’s do the same. The viruses we study hijack well-studied cellular pathways that might make an effective target for future therapeutic strategies.”

Calcium spike

In a healthy neuron, mitochondria move throughout the cell’s elongated, tree-like structure to provide energy for various processes that occur throughout the cell. For the strenuous task of long distance intercellular communication, mitochondria move along the axon and synapses, sites of cell-to-cell contact where signaling occurs.

Calcium plays a key role in this cell communication, Kramer explains. A neuron experiences a spike in calcium levels in the axon and synapses when it receives a signal from another neuron. Though a natural rover, mitochondria contain a protein called Miro that detects this rush of calcium and stops the organelles in the synapse. The mitochondria then provide energy as the cell passes a signal along to the next neuron.

In the latest research, Kramer and Enquist found that this spike in electrical activity floods the axon and synapses with calcium. As a consequence, the Miro proteins detect the increase in calcium and stop mitochondrial motion. The virus’ control over the cell immediately dropped off, however, when Kramer and Enquist interfered with Miro’s ability to respond to the uptick in calcium levels. Though the viral infection was not completely disrupted, it could not spread within or to other cells with the same efficiency.

Based on these observations, Kramer and Enquist suggest that viruses such as HSV-1 and PRV may bring mitochondria to a standstill in order to hijack their transportation. Mitochondria move about the neuron on the backs of motor proteins dynein and kinesin-1. During viral infection, mitochondria shed these proteins to stop moving when Miro detects an upsurge in cellular calcium.

“To disrupt the loading of mitochondria to motor proteins so that virions [complete virus particles] can load instead is a clever way for a virus to be transported and is a great new idea provoked by this data,” Alwine says.



I know - the cruelty is horrific and saddening

Actually this is why I am vegetarian..I cannot endorse cruelty on this scale. It has less to do with climate change than the horrific cruelty of the animal industry.

Scientists Use Machine Learning to Listen to Nature

This is very cool:

https://grist.org/climate/these-scientists-are-using-machine-learning-to-listen-to-nature-literally/

The United Nations has called on the world to protect 30 percent of the planet from human activity to help protect ecosystems and slow down climate change. But conservation areas are often vulnerable to illegal logging, poaching, mining, and other activities that threaten biodiversity. How can land managers detect these kinds of human impacts on protected ecosystems? Scientists are applying machine learning to identify human influence on the environment by literally listening to the environment — that is, by monitoring forest “soundscapes.”

Every ecosystem has its own distinctive collection of sounds that change with the season and even the time of day. According to Bryan Pijanowski, soundscape ecologist and director of Purdue University’s Center for Global Soundscapes, “Sounds are part of the ecosystem, and they are signatures of that ecosystem.” The unique sound environment of an ecosystem is known as a soundscape, the aggregate of all the sounds — biological, geophysical, and anthropogenic — that make up a place.

Sound has long been used by soundscape ecologists to assess biodiversity and other metrics of ecosystem health. Pijanowski has his own, informal rule of thumb: “If I can tap my foot to a soundscape, I know it’s fairly healthy,” he says, because it means “the rhythmic animals — the frogs and the insects, the base of the food chain — are there.”

Detecting human activity that impacts ecosystem health, like illegal logging and poaching, has long been a challenge for land managers and scientists, often requiring expensive and time-consuming surveys in which specialists manually identify species. But this new method requires only basic audio equipment that allows for remote monitoring of the soundscape, which can be done in real time, and a machine learning algorithm that listens for sounds that aren’t typical in a forest environment. “Say that there’s weird things going on or illegal activity, like guns being shot, or chainsaws from illegal logging,” explained Sarab Sethi, a mathematician at Imperial College London and the lead author of the new paper. “We work under the assumption that illegal activity contains a lot of anomalous sounds that are different from whatever usual sounds are in the ecosystem.”

How does the computer identify strange sounds? The key is unsupervised machine learning, meaning machine learning that doesn’t require human input to “train” the model on pre-identified data. “The way that we measure similarities and differences in sound is really the technical advance from our work,” Sethi told Grist. This new method uses a neural network to compare the “fingerprints” of sounds — not only their frequencies, but the structure of how their frequencies change over time — to one another other. “Once we’ve got a fingerprint, like a bird calling — a bird calling is more similar to a different species of bird calling, in this fingerprint, than it is to, say, a gunshot,” says Sethi. The neural network learns which sounds are typical of a healthy forest environment, and which ones are out of the ordinary.

The unsupervised technique requires less work from humans to identify sound; it’s also more robust than so-called supervised machine learning.



Paper abstract
Significance
Human pressures are causing natural ecosystems to change at an unprecedented rate. Understanding these changes is important (e.g., to inform policy decisions), but we are hampered by the slow, labor-intensive nature of traditional ecological surveys. In this study, we show that automated analysis of the sounds of an ecosystem—its soundscape—enables rapid and scalable ecological monitoring. We used a neural network to calculate fingerprints of soundscapes from a variety of ecosystems. From these acoustic fingerprints we could accurately predict habitat quality and biodiversity across multiple scales and automatically identify anomalous sounds such as gunshots and chainsaws. Crucially, our approach generalized well across ecosystems, offering promise as a backbone technology for global monitoring efforts.

Artificial (Abiotic) Energy Source for Molecular Motors

I posted a thread yesterday about molecular motors:
https://www.democraticunderground.com/122870647

Molecular motors are nanomachines inside the cell that use the chemical energy (in the form of ATP) produced by food (1 molecule of glucose produces some 30 odd molecules of ATP) to generate force and movement. They carry out a variety of functions ranging from vesicle transport to muscle contraction.

That was a motor molecule called Kinesin.

This is a different one called Myosin which is found in muscle cells and powers muscle contraction.



(Image credit: https://bau.seas.upenn.edu/. The Bau lab at UPenn. The Myosin isoform involved in muscle contraction is Myosin II.The Myosins shown there however, are Myosins V and VI, which are involved in vesicle/organelle transport).

Scientists have characterized various Myosins (there is a whole family of them) at the molecular level pretty thoroughly - its step-size (which is on the scale of nanometers. For comparison a single hair strand is about 17000-181000 nanometers in diameter), the energy consumed per step (about 1 ATP I think but I am not sure), force produced (which is on the scale of pico Newtons - for comparison the force needed to pick up a weight of 1g against gravity is 10^10 times that).

In the latest edition of the Biophysical Journal there is an article about an artificial energy source for muscle, which will help us advance our understanding of myosin further.


https://www.sciencedaily.com/releases/2020/07/200713165558.htm


Muscle physiologists sought an alternative energy source to replace the body's usual one, adenosine triphosphate (ATP). Such a source could control muscle activity, and might lead to new muscle spasm-calming treatments in cerebral palsy, for example, or activate or enhance skeletal muscle function in MS, ALS and chronic heart failure. They report this month that they have made a series of synthetic compounds to serve as alternative energy sources for the muscle protein myosin.

This month, the researchers report in the Biophysical Journal that they have made a series of synthetic compounds to serve as alternative energy sources for the muscle protein myosin, and that myosin can use this new energy source to generate force and velocity. Mike Woodward from the Debold lab is the first author of their paper and Xiaorong Liu from the Chen lab performed the computer simulation.

By using different isomers -- molecules with atoms in different arrangements -- they were able to "effectively modulate, and even inhibit, the activity of myosin," suggesting that changing the isomer may offer a simple yet powerful approach to control molecular motor function. With three isomers of the new ATP substitute, they show that myosin's force- and motion-generating capacity can be dramatically altered. "By correlating our experimental results with computation, we show that each isomer exerts intrinsic control by affecting distinct steps in myosin's mechano-chemical cycle."

DV recalls, "My lab had never made such types of compounds before, we had to learn a new chemistry; my student Eric Ostrander worked on the synthesis." The new chemistry involves sticking three phosphate groups onto a light-sensitive molecule, azobenzene, making what the researchers now call Azobenzene triphosphate, he adds.

The next stage for the trio will be to map the process at various points in myosin's biochemical cycle, Debold says. "In the muscle research field, we still don't fully understand how myosin converts energy gain from the food we eat into mechanical work. It's a question that lies at the heart of understanding how muscles contract. By feeding myosin carefully designed alternative energy sources, we can understand how this complex molecular motor works. And along the way we are likely to reveal novel targets and approaches to address a host of muscle related diseases."




This is the original article:
https://www.cell.com/biophysj/fulltext/S0006-3495(20)30500-2


Edit: Thanks are owed to eppur_se_muova for catching an error in the original message.

Crowding Stalls Traffic in Cells Too!

Though apparently only for teams of motors and not individual motors.


A Kinesin Motor Stepping Along a Microtuble. Image credit: Tom Snelling, UK. An earlier version of this post did not credit the source. It was an oversight.

https://phys.org/news/2020-07-effects-cellular-crowding-cell.html

As many diseases, including neurodegenerative diseases such as Alzheimer's, have been linked to the defective functioning of motor proteins in cell transport systems, understanding the intricacies of how motor proteins work in their native crowded cell environments is essential to understanding what goes wrong when they function incorrectly. Molecular motors are specialized proteins that bind to a variety of organelles, referred to as cell cargo, and transport them along microtubule filaments (structural proteins commonly referred to as the highway of the cell). Motor proteins often work in groups, binding to one cargo and inching together along the filament's path in the cell.

In the recent study Macromolecular crowding acts as a physical regular of intracellular transport, published in the journal Nature Physics, lead researcher and Assistant Professor of Physics at NYU Abu Dhabi George Shubeita and his team present the findings that in a native cell environment, which is crowded with a high concentration of macromolecules, the crowding significantly impacts the speed of groups of motor proteins, but not singular motor proteins. Motor proteins have been isolated from cells and studied in a laboratory setting, but this is the first time that cargo carried by motor proteins have been studied both in their native cell and in a setting that imitates the crowded cellular environment.

To simulate the crowded nature of cells, bovine serum albumin (a serum concentrated with proteins) was applied to glass slides, in addition to the kinesin motor proteins and microtubule filaments. Utilizing the laser light of optical tweezers to probe the movement of single motors and groups of motors, it was found that in more crowded environments, motors were more likely to fall off the filament when opposed. A group of motors would therefore be set-back each time a singular motor fell from the guideway. Even though groups of motors are shown to slow down in native cell environments, they are commonly used to carry cargo over long distances and overcome hindrances they face in a crowded cell by sharing the load, which singular motors cannot do.


For some background, motor proteins are molecular motors which use chemical energy (derived by hydrolysing ATP) to produce force and movement:

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

https://tomsnelling.co.uk/cell-biology/motor-proteins-traffic-on-the-cellular-highway/


This is the original article in Nature Physics:
https://www.nature.com/articles/s41567-020-0957-y
Macromolecular crowding acts as a physical regulator of intracellular transport

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