Reading Reaction Journal # 3

Arsenic anticancer target revealed

Researchers from China and France believe they have uncovered the molecular mechanism by which arsenic trioxide kills certain cancer cells. Arsenic is a poisonous metalloid that has been used in Chinese medicine for centuries to treat illnesses such as psoriasis and syphilis. More recently it has been shown to be effective against acute promyelocytic leukaemia (APL), a cancer of the blood.

However, the role that arsenic plays in the sequence of reactions leading to the death of the cancer cells has not been clear. Now, Xiao-Wei Zhang, from the Shanghai Institute of Hematology, and colleagues believe they have pinpointed the key target of the arsenic compound, although a detailed mechanism of action has still to be established.

It has been known for some time that in APL a genetic mutation results in the production of a rogue 'fusion protein' called PML-RAR which is vital to the survival of the cancer cells. Arsenic trioxide triggers a cellular protein called SUMO to 'tag' the fusion protein, earmarking it for destruction. The destruction of the protein leads to the death of the cancer cell, but until now, how As₂O₃ achieves this had remained a mystery.

The new research has shown that when As₂O₃ is added to cell extracts containing the fusion protein, the protein becomes insoluble and that the arsenic is associated with the insoluble fraction. The team then isolated a particular region of the PML protein called a zinc finger and showed that arsenic binds to this region, which is rich in cysteine residues. The researchers say that the binding of arsenic to this region causes several protein molecules to join together as an oligomer through cross-linking and conformational changes. The altered protein is then bound by SUMO, resulting in the protein aggregate's subsequent degradation. Team member Xiao-Jing Yan believes that knowing the target protein of the arsenic could allow better treatments to be devised in tandem with other drugs that also hit the same protein.

Arsenic trioxide has been used in medicine for centuries, but only now are the mysteries of how it kills cancer being solved © Science

'These exciting observations suggest that arsenic may be acting directly on the PML-RAR fusion protein to enhance its SUMO modification and thus provide the trigger for its destruction,' says Ron Hay of the University of Dundee in the UK, who has studied the role of SUMO in arsenic-induced degradation of PML.

'However the precise mechanism that allows arsenic to substitute for the zinc already bound to PML and how this brings about increased SUMO modification remains to be determined,' Hay continues. 'Clearly this will be a hot topic for future research and may reveal how arsenic, which binds to many proteins, has this remarkably specific activity on PML-RAR.'

References
Hadlington, S. (2010, April 08). Arsenic anticancer target revealed. Chemistry world.Retrieved April 26, 2010. From: http://www.rsc.org/chemistryworld/News/2010/April/08041002.asp

Vocabulary
Molecular: the smallest unit into which a substance can be divided without chemical change, usually a group of two or more atoms
Arsenic: a very poisonous substance, used to kill rats (= animals like mice, but larger) and harmful insects
Metalloid: a chemical element with some of the properties of a metal and some of a non-metal, for example silicon and arsenic
Sequence: a series of related things or events, or the order in which they follow each other
Pinpointed: to find out or say the exact position in space or time of something
Destruction: when something is destroyed
Cysteine: an amino acid containing sulfur that is found in most proteins; oxidizes on exposure to air to form cystine
Modification: a change to something, usually to improve it
Degradation: when the beauty or quality of something is destroyed or spoilt
Cellular: made of small parts
Zinc: a bluish white metal that is used in making other metals or for covering other metals to protect them
In tandem: If two pieces of equipment, people, etc. are working in tandem, they are working together, especially well or closely

Summary
China and France’s researchers have found that molecular mechanism from arsenic trioxide can kill certain cancer cells. Arsenic is a poisonous metalloid, but Chinese medicine has used it for centuries to cure illnesses; that is why people research arsenic’s efficacy. Recently, researchers have discovered it can be fight APL. However, they still do not understand which arsenic leads to the death of cancer cells. Arsenic trioxide triggers a cellular protein, and then we know the destruction of the protein results in the death of cancer; however we still do not know how As2O3 did this. Scientists have uncovered a particular region of PML protein that arsenic binds to this region, which is rich in cystic residues. Scientists also consider arsenic may act directly on the PML-RAR fusion protein and thus provide the trigger for its destruction. The precise mechanism still needs to be determined, but in the future arsenic will be a hot topic.

Reaction
Arsenic is a poisonous metalloid, and Chinese medicine just uses it to treat some illnesses, which are visible on the skin. Now Scientists want to know why the destruction of the protein leads to the death of the cancer cell, and how As2O3 achieves this, but it is still a mystery now. In my memories, the mechanism of arsenic endostain is the same as moss, which has poison. “When As2O3 is added to cell extracts containing the fusion protein, the protein becomes insoluble and the arsenic is associated with the insoluble fraction.” This is very important information for the human because we can make sure how to make drugs to treat people who have APL. I never tried arsenic because it is so dangerous. However, when I finished reading the article, I have an idea that I want to become the person who treat people’s illness with arsenic.

Reading Reaction Journal # 2

Silver sputtered nano chips mimic brain synapse

US researchers aiming to emulate the functionality of a cat's brain have developed an easily-fabricated, robust nanoscale device that imitates the connectivity between neurons in the brain.

The two-terminal electronic device, known as a memristor ('memory' + 'resistor'), is similar to a biological synapse in that its conductance can be precisely changed by controlling the charge running through it. The researchers found that changing the way they embedded silver ions in the silicon-based devices improved their performance.

A memristor's resistance is controlled by its 'memory' of the currents and voltages it has been exposed to. 'It can be employed to build a computer in the way that nature builds brains,' explained Wei Lu of the University of Michigan, Ann Arbor.

The first memristor was made in 2008 from titanium dioxide, which is difficult to integrate with traditional silicon computer chips. Silicon-based devices have since followed, although the resistance change is abrupt. Now Lu's team has produced silicon memristors that work more smoothly. 'The new design emulates biological systems better because the change is more gradual and can be more precisely controlled,' he says.

In the memristor, current flow is associated with ion motion, changing its resistance as they move. Previous memristors introduced silver ions to perform this function into the silicon from an electrode deposited on top. However, this process carves localised conduction channels responsible for the abrupt changes.

How memristors can act as synapses between neurons, with schematics of the memristor structure and the two-terminal device in the insets. © Nano Letters, American Chemical Society

Instead, Lu's students Sung-Hyun Jo and Ting Chang introduced silicon and silver simultaneously via co-sputtering. Using an argon plasma, they ejected atoms from pure elemental targets into a vacuum chamber containing the partially-fabricated memristors. The atoms deposit onto the device in a 20-30nm thick film, allowing easy control over the ratio between the two components. 'The device can endure at least 150 million write and erase cycles,' Lu told Chemistry World. 'When you write and erase other systems a few thousand times, performance typically starts to degrade.'

Memristors can simulate synapses because electrical synaptic connections between two neurons can seemingly strengthen or weaken depending on when the neurons fire. Lu and colleagues demonstrated that their memristor performs an equivalent function with a conventional silicon-based circuit acting as neurons, raising and lowering the memristor's resistance. The team is part of a US Defense Advanced Research Projects Agency programme that aims to create computers that mimic biological neural systems. 'These will be the components we will use to make the hardware version of a cat brain,' Lu said.

Nadine Gergel-Hackett, who researches memristor technology at the US National Institute of Standards and Technology, acknowledges the Michigan team's successful creation of a brain synapse analogue. 'This work is a large step towards the realization of biology-inspired computing,' she says.

References

Extance. A. (2010). Silver sputtered nano chips mimic brain synapse. Chemical Society, from http://www.rsc.org/chemistryworld/News/2010/March/04031001.asp

Vocabulary

Fabricate: to invent or produce (esp. a story that isn't true) in order to deceive.

Robust: (of a person, animal, or plant) strong and healthy, or (of food or drink) full of flavor.

Nanoscale: extremely small.

Imitate: to copy (someone's speech or behavior), or to copy (something) as a model.

Terminal: causing or ending

Ion: an atom that has a positive or negative electrical charge as the result of adding or taking away an electron

Emulate: to copy (someone's behavior) or try to be like (someone else) because you admire or respect them

Synapse: the point at which electrical signals move from one nerve cell to another

Schematic: showing the main form and features of something, usually in the form of a drawing, which helps people to understand it.

Silicon(Si): a common chemical element that is used in electronic devices, such as computers, and in making materials such as glass, concrete, and steel.

Ejected: to force (someone) to leave a particular place, or to send out (something) quickly and often with force.

Analogue: something which is similar to or can be used instead of something else.

Summary

This article talks about how scientists simulate brain synapses using nanoscale technology. In the article, the author mentions what the principle about memristor is. Before scientists used different materials to integrate with Si chips, but did not use silver nano chips. They get trouble with the resistance change fast, but it is still better than before. Instead, Sung-Hyun Jo and Ting Chang, who are Lu’s students from University of Michigan, use silicon and silver simultaneously via co-sputtering to solve the resistance problem and the memristor is almost like a brain synapse. Nadine Gergel-Hackett, who is very famous in this field, says: 'This work is a large step towards the realization of biology-inspired computing.'

Reaction

I was deeply attracted by this article when I read it, because I am very curious about the brain; it is a very mysterious field that I hadn’t touched before. Now this article shows me about some new information about how to mimic a brain synapse.

I had already learned about brain synapse when I studied in high school. A synapse is the only one way to input a neural signal, and in the central nervous system, the neurons use the synapses’ form to connect to each other, and then become a complex neural network. That is difficult to mimic. However, in 2008, the first memristor was made. This invention brought the dawn of the scientists. They want to solve a lot problems because we just at the low level in the field of nervous system. However, Sung-Hyun Jo and Ting Chang used the most common materials for computer chips, which are silicon and silver, the raw materials for memristor. I think the metal electrode is the same as two neurons, while filling in the middle of the silicon and silver can seem the synaptic, and then with the current, it will flow from anode to negative electrode. If I suppose the time for the current is 20ms, then I will know the current between two electrodes is 40ms time delay, and signal will be saved in memristor. This is just my inference. I do not understand how I can know the signal is saved because the time is so short that we cannot record it.

This article tells me about how to simulate a brain synapse with silver sputtered nano chips. This technology can change humans’ life because computers and robots will have similar neurotransmitters as humans. This technique will be able to bring happiness for humans at the same time it may bring disaster for humans too. Because they can control by themselves, and people cannot stop them. If they want to destroy human beings, humans will have a big trouble.