Biomolecular machines

[Phronesis]

Design Features of a Mitotic Spindle: Balancing Tension and Compression at a Single Microtubule Kinetochore Interface in Budding Yeast​

Accurate segregation of duplicated chromosomes ensures that daughter cells get one and only one copy of each chromosome. Errors in chromosome segregation result in aneuploidy and have severe consequences on human health. Incorrect chromosome number and chromosomal instability are hallmarks of tumor cells. Hence, segregation errors are thought to be a major cause of tumorigenesis. A study of the physical mechanical basis of chromosome segregation is essential to understand the processes that can lead to errors. Tremendous progress has been made in recent years in identifying the proteins necessary for chromosome movement and segregation, but the mechanism and structure of critical force generating components and the molecular basis of centromere stiffness remain poorly understood.

During cell division, DNA is replicated and commitment to this process is started during the G1/S phase. During the S-phase, DNA is replicated and cells grow (take up energy) in size in order to provide enough energy for daughter cells. Transition from the S-phase into the G2 phase is characterized by the completion of the replication process and initiation of the mitotic spindle apparatus. It is during this phase that accurate segregation of duplicated DNA is crucial in order to prevent downstream aberrations.
Parts of this apparatus include:
Spindle Pole Bodies (microtubule organizing centers): Responsible for organizing microtubules into two poles.
Microtubules: Tubelike polymer structures playing an essential role in the structure of the spindle formation as well as providing conduits to transmit information.
Microtubule Motor Proteins: Including kinesin and dynein motors: These motors are required for bipolar spindle formation, spindle positioning, metaphase spindle stability, and anaphase progression.
Microtubule-Associated Proteins: Regulates microtubule polymerization dynamics. (rescue vs catastrophe).

Each time this apparatus is assembled it goes through the following checkpoints before initiation of mitosis (final stage cell division):
1) Spindle formation
2) Establish correct connections between chromatids, microtubules, spindle pole bodies and motor proteins.
3) Recognize and correct incorrect attachments
4) Regulate microtubule dynamics

Other processes check and control DNA integrity, and only once the the integrity and structure of DNA is intact, does it signal for the mitotic spindle aparattus to initiate mitosis.

All this happens while the cell monitors nutrient availability and other stress signal in order to correctly respond to stress situations. The cell division can be shut down for repairs and if repairs are not succesful or stress sitations are too much, the cell goes into conservation mode (autophagy) or self destructs (apoptosis or necrosis), depending on the environmental signal.
All exquisitely controlled processes present in all eukaryotes.

 

[Phronesis]

New Insight Into Architecture Of Cellular Protein Factories: Efficient Working In Confined Spaces

ScienceDaily (Jan. 22, 2009) — Each cell in an organism possesses its own protein factories known as ribosomes. Every second, these enzyme complexes produce new proteins with messenger molecules (mRNA) from the cell nucleus as blueprints. In order to generate as many proteins as possible at the same time, several ribosomes cluster together to form an “industrial complex” – the polysome - and read simultaneously the same messenger molecule.

Even simple bacterial cells can be viewed as computers that are able to manipulate information (nano-intentionality). In order to see how these protein factories monitor and manipulate information for improved fidelity in protein formation, read here.

The article continues:

Scientists at the Max-Planck-Institute of Biochemistry have now, for the first time, been able to reveal the three-dimensional structure of these complexes.

In a polysome, the ribosomes are densely packed and exhibit preferred orientations: The small ribosomal subunits are orientated towards the inside of the polysome and the ribosomes are arranged either in a staggered or in a pseudo-helical structure. This arrangement ensures that the distance between nascent protein chains is maximized, thereby reducing the probability of intermolecular interactions that would give rise to aggregation and limit productive folding. Until now, the belief has been that specialised proteins, the so-called chaperones, would prevent protein misfolding.

Against the background of the new findings, their function appears in a new light: “It appears possible that the main function of chaperones that interact with nascent polypeptide chains is not to suppress chain aggregation within polysomes, but rather to reduce intra-chain misfolding as well as aggregation between different polysomes in the crowded cellular environment”, explains Ulrich Hartl, head of the “Cellular Biochemistry” department, who lead the project in cooperation with Wolfgang Baumeister, head of the “Molecular Structural Biology” department.

Moreover, the spatial structure of the polysome enables the ribosomes to process the messenger molecule in the protected area within the polysome and to pass it on without detours. Thus, the architecture of the cellular protein factories facilitates an optimized work flow and increases the efficiency of protein folding.

Machines folding machines into place like they are supposed to function. Beautiful...

 

[Phronesis]

Immune System: Decoding The Language Of Memory Cells

ScienceDaily (Jan. 23, 2009) — When an infection attacks, the body's immune system sounds the alert, kills the invading germs and remembers the pathogen to protect against contracting the same type of infection again. Exactly how immunological memory develops is a mystery just beginning to be unveiled by Emma Teixeiro, PhD, in an article published in the journal Science.

The key finding is that a distinct program generates the memory cells that protect an individual against re-infection. This current work uncovers some of the language that is necessary to start this program, said Teixeiro, assistant professor of molecular microbiology, immunology and surgery at the University of Missouri School of Medicine.

A genetic program with a distinct language that generates a state against future infections. The state is representative of the actions of memory cells and their ability to manipulate information.

How?

Teixeiro cites vaccination as the most practical example of how to generate cells that remember infections. With a single shot, the body is infected with a small dose of a pathogen, so the next time the body is exposed, it immediately recognizes the invader and fights it off, preventing disease.

"When the human body is infected, T cells recognize the pathogen with a specific receptor and kill the infection," Teixeiro said. "But once the infection has been cleared, a small number of cells survive. These are the memory T cells."

Teixeiro's lab used a mouse model to test how communication inside a T cell would affect a body's ability to fight infection. Two groups of mice – some with normal T cells and others with a mutation in their pathogen receptor – were infected with listeria monocytogenes, a bacterium often associated with food-borne illness in humans. Both groups of mice fought off the infection equally well, but those with the cell mutation were not able to generate memory T cells to protect against future infection due to a disruption in certain signals within the cell.

"A person with this cell mutation would not develop memory T cells. If we knew what was necessary to generate these memory cells, we would not need to worry about fighting the same infection over and over again," Teixeiro said, noting a direction for continued research. "We are currently figuring out which signals are important for memory generation and protection. This is important for improving vaccines and tumor immunotherapies."

So, the immune system makes use of evolutionary processes to design optimal antibodies and as soon as it hits an optimum design it stores the information to protect the system from future infections... foresight.

 

[alloytoo]

the immune system makes use of evolutionary processes to design optimal antibodies[/URL] and as soon as it hits an optimum design it stores the information to protect the system from future infections...

Here's an interesting post on the immune system.

Contrary to popular belief, HIV-1 patients actually have a hyperactivated immune system. See, HIV-1 likes to infect CD4+ T-cells, specifically, activated CD4+ T-cells. It wants to activate your immune system so it has more 'food'.

This immune system hyperactivation doesnt just mean more HIV-1 targets-- eventually, immune cells just die from exhaustion (programed apoptosis). For an example of how bad this is-- lets say your body kept some memory immune cells around from a cold you got when you were seven. If you get exposed to that particular cold virus again, your immune system pounces on it before you can even get sick. YAY! But if your immune system is in a hyperactive state, and those memory cells die from exhaustion without leaving any more 'baby' memory cells... the next time you get exposed to that cold virus, youve got to mount a whole new immune response. While that wouldnt be so bad for you or me, if you are an AIDS patient with not a lot of immune cells around anymore to attack that cold, or if youre an HIV-1 patient with lots of CD4+ T-cells, but they arent responsive... WHAMMO.

 

[Phronesis]

Here's an interesting post on the immune system.

Just goes to show you how viruses can use evolution to bypass or hijack good working immune systems and then make it go completely haywire. Like throwing a nut in a functioning engine. Stay away from nuts .

Remember this poseur and how he said how much nonsense the genome contains? Phew luckily he is retired now and hopefully won't be making any more arguments from ignorance (really the only kind he had). Science moves on and leaves the poseurs to wallow in their ignorance:
New Class Of Small RNAs Discovered: Function Defined

The research, which is part of a multinational project called ENCODE, also provided information concerning the biological function of the new short RNA class.

The team's findings, which appeared online January 25th, ahead of print, in the journal Nature, significantly improve our understanding of how functional information is stored in the genome. The work at CSHL was spearheaded by Professors Thomas Gingeras, Ph.D., a leader of ENCODE, and Gregory Hannon, Ph.D., a world-renowned expert in small RNAs.

These results are a good illustration of why the ENCODE project was established," says Dr. Gingeras. "They show how collaborative projects can reveal functional elements and mechanisms embodied in the genome that have never before been described."

And thought to have been nonsense by some posers .

Exploring vast, non-coding regions of the genome

At the conclusion of the Human Genome Project in 2003, scientists published a final draft of the DNA sequence found within healthy human cells – an assemblage of roughly 3 billion "As" "Ts" "Cs" and "Gs." While justifiably proud of the feat, genome scientists knew that the most interesting part of their task was just beginning.

Using the published 2003 sequence, they were able to specify across the entire genome which stretches of DNA comprised genes – regions that act as blueprints for the manufacture of proteins. To the surprise of many, those regions accounted for only about 2% of the genome. Following that realization, most of the remaining 98% began to look more like terra incognita than conquered territory.

To define the full set of genomic elements that perform functions in living cells and to hunt down their location amidst the thicket of genes and non-coding DNA, a multinational project known as ENCODE (an acronym for Encyclopedia of DNA Elements) was initiated in 2003. Recent research by Professor Gingeras, who has played a major role in the project, has revealed that nearly all of the genome is converted into various types of RNA molecules, a process once thought to be restricted to protein-coding genes. What roles, if any, each of these new types of RNA play within the cell is now an important topic of research.

Imagine if people believed they really were pointless nonsense of the genome...

 

[Phronesis]

Key Component In Cell Replication Identified

ScienceDaily (Jan. 29, 2009) — Last week, a presidential limousine shuttled Barack Obama to the most important job in his life. Scientists at the Stanford University School of Medicine have now identified a protein that does much the same for the telomerase enzyme — ferrying the critically important clump of proteins around to repair the ends of chromosomes that are lost during normal replication. Without such ongoing maintenance, stem cells would soon cease dividing and embryos would fail to develop.

"This is the first new protein component of telomerase that has been identified in 10 years," said Steven Artandi, MD, PhD, associate professor of hematology. "And it's likely to be a valuable target for anti-cancer therapies."

Telomerase is normally expressed in adult stem cells and immune cells, as well as in cells of the developing embryo. In these cells, the enzyme caps off the ends of newly replicated chromosomes, allowing unfettered cell division. Without telomerase, cells stop dividing or die within a limited number of generations. Unfortunately, the enzyme is also active in many cancer cells. Artandi and his collaborators found that blocking the inappropriate expression of the protein, called TCAB1, in human cancer cells keeps telomerase from reaching its DNA targets, called telomeres, and may limit the cell's life span.

Prior to this study, TCAB1 had no known function. "Andy [Venteicher] found that TCAB1 binds not only telomerase, but also a specific class of small, non-coding RNA molecules that also end up in the Cajal bodies," said Artandi. He added that the protein may be a common biological shuttle responsible for delivering a variety of molecules to their destinations. He and his collaborators plan to continue their study of TCAB1 and also to identify other telomerase components.

Shuttling machines at the molecular level with the function of delivering crucial components needed for successful self-replication.

"This is a story that's been unfolding over decades," said Artandi. "Telomerase is such a high-priority target for many diseases, but it's hard to attack when you know very little about it. But that's changing now."

Exciting times...


Now this too:
Human DNA Repair Process Recorded In Action

ScienceDaily (Jan. 28, 2009) — A key phase in the repair process of damaged human DNA has been observed and visually recorded by a team of researchers at the University of California, Davis. The recordings provide new information about the role played by a protein known as Rad51, which is linked to breast cancer, in this complex and critical process.

Similar components exist in bacterial cells.

With the ability to watch the assembly of individual filaments of Rad51 in real time, Kowalczykowski's team made a number of discoveries. Among those are that, in contrast to their bacterial counterparts, Rad51 filaments don't grow indefinitely. This indicates that there is an as-yet undiscovered mechanism that regulates the protein's growth, Kowalczykowski said.

 

[Phronesis]

Phytoplankton Cell Membranes Challenge Fundamentals Of Biochemistry

ScienceDaily (Feb. 2, 2009) — Get ready to send the biology textbooks back to the printer. In a new paper published in Nature, Benjamin Van Mooy, a geochemist with the Woods Hole Oceanographic Institution (WHOI), and his colleagues report that microscopic plants growing in the Sargasso Sea have come up with a completely unexpected way of building their cells.

Until now, it was thought that all cells are surrounded by membranes containing molecules called phospholipids – oily compounds that contain phosphorus, as well as other basic biochemical nutrients including nitrogen. However, Van Mooy and his colleagues from WHOI, the University of Southern California, University of Hawaii, the Czech Academy of Sciences, the Bermuda Institute of Ocean Sciences, University of Southern Maine, and the Centre d’Océanologie de Marseille have found phytoplankton in the Sargasso Sea that make their cell membranes without using phospholipids, using non-phosphorus-containing ‘substitute lipids’ instead. These substitute lipids were once regarded as merely a molecular peculiarity of phytoplankton grown in the laboratory, but are now recognized to be used by phytoplankton throughout the world’s ocean.

It would be interesting to understand the intracellular mechanism of manufacturing of these new types of membranes.

Substitute lipids “are the most abundant membrane molecules in the sea and they were essentially unknown until now,” says Van Mooy, whose work at WHOI was supported by the National Science Foundation, the Office of Naval Research, and the WHOI Ocean Life Institute. The finding could help rewrite the fundamentals of cell biochemistry.

These betaine molecules have structures that resemble amino acids, the building blocks of proteins. But unlike the cyanobacterial SQDG, the betaine lipids require nitrogen. The more structurally sophisticated plants have dodged the phosphorus requirement, but they still have to have nitrogen.

Van Mooy thinks he’s on to something fundamental about the ways that phytoplankton survive in the ocean. Of his future research working out the dynamics of the membrane lipid substitutions Van Mooy says, “You could think of it like a tool. Something very basic. Maybe there is an underlying principle here that we will uncover.” Hold the presses on the textbooks until they do.

Ah, the scientific view that something fundamental, an underlying principle will be discovered. That is the nature of science... the pursuit of fundamental truths. Truth: A mental construct.

 

[Phronesis]

How A Cell’s Mitotic Motors Direct Key Life Processes

ScienceDaily (Feb. 3, 2009) — In a cleverly designed experiment, cell biologists have discovered how dyneins organize chromosome placement to prepare for cell division. The surprise finding suggests it’s the motor domain of the nanoscale chemical engine, not the cargo domain as once believed, that directs pre-mitotic action.

University of Massachusetts Amherst biologists have discovered a secret of how cells organize chromosomes to prepare for dividing. Their unexpected finding was recently reported in the journal, Current Biology.

The experiments sought to reveal how the cell’s tiny, two-part chemical engine known as dynein, just 40 nanometers in diameter, takes charge of mitosis and keeps the delicate strands of chromosomes in order and in position. Until now, cell biologists had assumed it was the dynein’s cargo domain that regulated this process. UMass Amherst cell biologist Wei-lih Lee and colleagues showed that it is the motor domain instead.

Dynein, like a delivery truck, carries cargo, Lee explains, but this protein truck is specialized because it interacts chemically and physically with the road. In the cell, this means dynein travels along segments of polymeric microtubule “roads” that grow and shrink as needed by adding or dropping sections. From experiments in budding yeast, Lee, with a talented postdoctoral fellow, Steven Markus, and biology junior fellow Jesse Punch, found that “dynein has a preference for locating at the ends of these microtubule tracks.”

Lee says a lot of credit for a cleverly designed and executed set of experiments goes to Markus, who cut the dynein engines into motor and cargo halves and challenged the yeast cells to divide with access to only one part of the protein at a time. Markus also designed brighter-than-usual fluorescent probes to attach to the two dynein parts, red for the engine, green for the cargo domain. The strategies worked. The UMass Amherst research team now has one of the most elegant and practical probes for studying dynein function. Lee says, “I’m already getting requests from other researchers who want to use our new probes.”

In this system, they observed that like a moving walkway at the airport, “dynein is a smart truck because it parks at the end of the microtubule, and ‘rides’ along as the track grows,” Lee explains. “Our findings show that the dynein’s motor domain, the engine’s core, is responsible for this end-binding property, which is surprising given that the same domain is used for walking along the track.”

Applying their new understanding to cell division, the researchers say, “our findings further suggest that the dynein engine is turned off when it is parked on the microtubule end, but then turned on upon reaching the proper attachment site in the daughter cell’s wall,” says Lee. “This mechanism allows the yeast cell to control dynein activation with high accuracy” and avoids potential problems of transporting an “activated” protein through the cell.

Results of this new knowledge in basic science are also relevant for human nerve cell function. “It has already been shown that nerve cells use the same mechanism as yeast does to move the cell body,” says Lee. Dynein malfunction can lead to mistakes in nerve cell migration which causes poor brain development disease such as lissencephaly.

Clever Design.

 

[rwenzori]

Clever Design.

One assumes you are referring to the "cleverly designed and executed set of experiments", as there is no other evidence of design that I can see. Or are you positing a variation on the tired old argument that the eye is evidence of god?

 

[Phronesis]

One assumes you are referring to the "cleverly designed and executed set of experiments", as there is no other evidence of design that I can see. Or are you positing a variation on the tired old argument that the eye is evidence of god?

Clever designed experiments (you still agree that was intentionally designed don't you?).
And clever how cells can prepare for future events (such as cell division) so they can be executed succesfully. Just like scientists prepare for experiments so they can be succesfully executed.
Afterall, cells are the designers of other cells, and cells are clever designs... computers that make computers

 

[rwenzori]

Clever designed experiments (you still agree that was intentionally designed don't you?).
And clever how cells can prepare for future events (such as cell division) so they can be executed succesfully. Just like scientists prepare for experiments so they can be succesfully executed.
Afterall, cells are the designers of other cells, and cells are clever designs...

Have they got minds?

 

[Phronesis]

Ah, here is a suggestion. Start a thread to sufficiently describe what you think "minds" are. Until you describe what you think "minds" are (in your own thread of course), that question will remain on ice.

Do cells have "minds"? They certainly have intrinsic nano-intentionality...

 

[rwenzori]

Ah, here is a suggestion. Start a thread to sufficiently describe what you think "minds" are. Until you describe what you think "minds" are (in your own thread of course), that question will remain on ice.

Do cells have "minds"? They certainly have intrinsic nano-intentionality...

I'll give an answer here I think.

The definition of "mind" is, as you are well aware, a vast field, but the brief start of the Wikipedia article on the subject could be a working definition for the purposes of this thread:

Mind refers to the aspects of intellect and consciousness manifested as combinations of thought, perception, memory, emotion, will and imagination, including all of the brain's conscious and unconscious cognitive processes. It may also include cognitive processes in non-human animals along with the conscious experiences that may accompany them. "Mind" is often used to refer especially to the thought processes of reason. Subjectively, mind manifests itself as a stream of consciousness.

"Nano-intentionality"? Old Tecumseh's concept, of which he said:

I provisionally dub the capacities in question "nano-intentionality": a microscopic form of "aboutness". The form of intrinsic intentionality I propose is thoroughly materialistic, fully compatible with known biological facts, and derived non-mysteriously through evolution.

You STILL don't understand the term "intentionality" do you LOL???

 

[Phronesis]

I'll give an answer here I think.

I asked nicely, please elaborate in your own thread. you are once again just trolling after being kindly requested not to.
Perception, memory, problem solving etc. All intrinsic properties in cells. But elaborate a bit more in your own thread so we can see if you actually understand what you just quoted...

"Nano-intentionality"? Old Tecumseh's concept, of which he said:



You STILL don't understand the term "intentionality" do you LOL???

With regards to intentionality, no-one has even attempted to explain how intentionality is derived. Try... in the correct thread please .

 

[rwenzori]

I asked nicely, please elaborate in your own thread.

in the correct thread please .

Lollers at your silly attempts to control!

I'll post where I like thanks!

You need a few more properties of "mind", and don't forget the bit about "brain" and "consciousness" either. Or do you think your mate Chalmers' panpsychism is right - rocks have minds etc??

 

[Phronesis]

Lollers at your silly attempts to control!

I'll post where I like thanks!

Please use the self-control instilled into you by your father and use it to elaborate on YOUR understanding of what YOU think "minds" are. Thanks.

 

[rwenzori]

Please use the self-control instilled into you by your father and use it to elaborate on YOUR understanding of what YOU think "minds" are. Thanks.

Do you have a problem with the working definition quoted? If so what? Or am I just requiring you to think outside of your own presuppositions, and that is hard for you?

 

[cyghost]

I asked nicely, please elaborate in your own thread.

Stop doing that. The question flowed naturally from the discussion. It is pertinent to *this* thread as it developed.

you are once again just trolling after being kindly requested not to.

He is not. He is discussing the topic and following its flow. You are making claims comparing scientists and cells. When asked if cells are conscious in other threads, you evaded the question.

Here you are evading again.

Instead of telling others what and where and how to post, answer the questions posed to you. Your need to control threads is irksome and you are never going to get your way. I suggest you stop doing it. Seriously.

 

[Phronesis]

Do you have a problem with the working definition quoted? If so what? Or am I just requiring you to think outside of your own presuppositions, and that is hard for you?

I can see you are incapable of creating a single coherent post where you actually attempt to elaborate YOUR understanding of a specific topic. Nice try to troll this thread. Not working though, people see right through you...

When a person sees a thread veering off topic as a result of discussion in a thread, there is nothing wrong about asking that particular part of the thread to be separated and discussed in its own thread in order to preserve the integrity of the original thread. So please, stop trolling and elaborate your thoughts in a new thread.

 

[rwenzori]

I can see you are incapable of creating a single coherent post where you actually attempt to elaborate YOUR understanding of a specific topic. Nice try to troll this thread. Not working though, people see right through you...

I would say you are the one people see right through, as you refuse to state your case and define your terms. That is a sign that you cannot comprehend things outside of others' thoughts that you quote-mine.