Preventing cancer development inside the cell cycle

 by Biomechanism 

Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have identified a cell cycle-regulated mechanism behind the transformation of normal cells into cancerous cells. The study shows the significant role that protein networks can play in a cell leading to the development of cancer. The study results, published in the October 21 issue of the journal Molecular Cell, suggest that inhibition of the CK1 enzyme may be a new therapeutic target for the treatment of cancer cells formed as a result of a malfunction in the cell’s mTOR signaling pathway.

In the study, NYU Cancer Institute researchers examined certain multi-protein complexes and protein regulators in cancer cells. Researchers identified a major role for the multi-protein complex called SCF^βTrCP . It assists in the removal from cancer cells the recently discovered protein DEPTOR, an inhibitor of the mTOR pathway. SCF (Skp1, Cullin1, F-box protein) ubiquitin ligase complexes are responsible for the removal of unnecessary proteins from a cell.

This degradation of proteins by the cell’s ubiquitin system controls cell growth and prevents malignant cell transformation. Researchers show that inhibiting the ability of SCF^βTrCP to degrade DEPTOR in cells can result in blocking the proliferation of cancer cells. In addition, researchers discovered that the activity of CK1 (Casein Kinase 1), a protein that regulates signaling pathways in most cells, is needed for SCF^βTrCP to successfully promote the degradation of DEPTOR.

“Low levels of DEPTOR and high levels of mTOR activity are found in many cancers, including cancers of the breast, prostate, and lung,” said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. “It is critical for researchers to better understand how the protein DEPTOR is regulated. Our study shows it would be advantageous to increase the levels of DEPTOR in many types of cancer cells to inhibit mTOR and prevent cell proliferation.”

The mTOR pathway (mammalian Target Of Rapamycin) regulates the growth, proliferation, and survival of a cell, and its proper regulation is essential to prevent the formation of cancer cells. DEPTOR interrupts the mTOR pathway by binding to mTOR protein complexes and blocking their enzymatic activities, restraining cell growth. This helps support the proliferation and survival of cancer cells.

Study experiments showed that a reduction of SCF^βTrCP and CK1 proteins in cells resulted in accumulation of DEPTOR. Also, DEPTOR was destroyed in cells only when SCF^βTrCP and CK1 were both present. Thus, inhibition of SCF^βTrCP or CK1 represents a novel and promising way to inhibit the mTOR pathway. A pharmacologic inhibitor of CK1 was tested by researchers and shown to successfully stabilize DEPTOR in cells, while other pharmacological agents had no effect.

“Our study findings demonstrate that DEPTOR is regulated by the protein complex in cells reentering the cell cycle, and deregulation of this event could contribute to the aberrant activation of the mTOR pathway in cancer,” said lead author Shanshan Duan, PhD, a post-doctoral fellow in the Department of Pathology at NYU School of Medicine in Dr. Pagano’s Laboratory. “This study suggests a novel approach to stop the deregulation of the mTOR pathway in cancer cells with promising small molecule inhibitors of CK1.This study is another step forward in the translation of laboratory findings into more effective approaches to cancer prevention and treatment.”

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This study was done in collaboration with the NYU Cancer Institute, Howard Hughes Medical Institute, The Lautenberg Center for Immunology, and Hebrew University in Israel.

2012 Toyota Hybrid I

Pig-to-Human Transplants Could Be Closer Than You Think

By Dan Nosowitz

Hog head, the deadliest food at the banquet fiskfisk, via Flickr.com

Two scientists at the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh discussed the state of xenotransplantation--the use of cells, organs, or tissue from one animal in another--in a review in The Lancet. In that review, they touch on the history of one particular subject: pig-to-human transplants. Their conclusion? Clinical trials of pig-to-human transplants could begin in just a few years.

Pigs that are genetically modified with genes to protect their organs and other inside bits from attack by the human immune system are capable of all kinds of potentially life-saving effects. Research has been conducted until now with non-human primates, and while these primates have not been able to survive for all that long with pig organs--at best, a pig heart-implanted primate survives for around eight months--that could be enough time to serve as temporary lifesavers. Cells and tissue could be used to counteract human diseases like diabetes (as inthis example) and Parkinson's, and have actually shown more success than complete organs.

The paper concludes by saying:

With new genetically modified pigs becoming available that are likely to improve the outcome of cellular and corneal xenotransplantation further, we believe that clinical trials will be justified within the next 2-3 years. No safety concerns that would prohibit such clinical trials have been reported...With regard to pig tissues and cells, as opposed to organs, it would seem that clinical xenotransplantation could soon become a reality.

The scientists believe that soon enough, genetically-modified pig organs could be even more capable than mechanical versions, which is surely great news for those who need them.

[via The Independent]

BE WATCHFUL WHEN YOU GIVE YOUR CREDIT CARD FOR PAYING YOUR BILL

How Comets In Distant Solar Systems Could Deliver Oceans to Exoplanets

By Rebecca Boyle

Cool, Clear Water The nearby star TW Hydrae has a burgeoning solar system with a sprawling cloud of cold water vapor. The vapor is cold enough to eventually form comets, which could deliver oceans to dry planets that are forming in the system. NASA/JPL-Caltech/T. Pyle

A pair of new comet studies from two space telescopes show how other planets might grow oceans. For the first time, astronomers have detected a ring of cold water vapor encircling a young star’s dusty planetary disk. And a separate study in a different star system shows ahailstorm of icy bodies could be bombarding a young planet. Together, the studies bolster a theory about how comets may have delivered Earth’s oceans — and they show this is not a unique occurrence in the universe.

Today's issue of the journal Science contains a paper describing cold water surrounding a young star called TW Hydrae, located in the Hydra constellation. Astronomers have previously found warm water around planet-forming regions, but not huge amounts of cold water. This cold reservoir demonstrates how comets form in a solar system’s outer reaches.

"Our observations of this cold vapor indicate enough water exists in the disk to fill thousands of Earth oceans," said astronomer and lead author Michiel Hogerheijde of Leiden Observatory in The Netherlands. TW Hydrae is just 10 million years old, and astronomers believe the dusty disk surrounding it will eventually coalesce to form planets. The frosty water vapor will probably coalesce to form comets, some of which might rain down on those new planets.

This does indeed happen in other solar systems, as a separate study shows. On Wednesday, astronomers using the cold-observing Spitzer space telescope described finding a dusty band around a star called Eta Corvi, a billion-year-old star system in the constellation Corvus, the crow. The band’s contents strongly match that of an obliterated comet, suggesting a massive collision, perhaps with a planet. This sounded like what happened during Earth’s own Late Heavy Bombardment. The system has a second, bigger ring much farther out, just like our own Kuiper Belt. And the bombardment is even happening around the same time that ours did, about a billion years after the Earth formed.

During the Late Heavy Bombardment here, a cascade of frosty space rocks rained down on the planet, delivering water and other things. (Earth was too hot after its formation to hold on to any native H2O.) Earlier this month, researchers using the European Space Agency’s Herschel Space Observatory said they found the chemical isotope signature of Earth water out in the distant reaches of our solar system, suggesting that Oort Cloud comets may have been one source of this bombardment, not necessarily just asteroids. This new Spitzer study suggests the same type of bombardment is happening at Eta Corvi.

So it sounds like comet clouds and water reservoirs are not uncommon at all. Perhaps around each star’s a pool of water — which could mean very interesting things for the search for extraterrestrial life.

A Barrage of Comets: This artist's concept illustrates a storm of comets around a star near our own, called Eta Corvi. Evidence for this barrage comes from NASA's Spitzer Space Telescope, whose infrared detectors picked up indications that one or more comets was recently torn to shreds after colliding with a rocky body.  NASA/JPL-Caltech

New Cutting Edges Pull Saw Blades Forward

By Max Fischer

Saws Jonathon Kambouris

Most saw blades don’t have the strength to chew through the compressed particle board that has become so common in construction. DeWalt and Bosch’s new blades, however, have extra teeth to grab the faux wood ahead of the cutting edge and literally pull the blade forward. The result: a more controllable slice that’s easier on workers’ arms.

THE TECH

DeWalt
As the DeWalt blade (left) works its way through cuts, eight resin-filled slots absorb the vibration that’s usually transferred to the arm of the person holding it. To help the blade glide easily across rough materials, DeWalt glazes the blade’s teeth with a Teflon-like coating.
DeWalt Precision Framing Blade: $10

Bosch
The Daredevil’s cutting edges (right) also have a nonstick coating to inhibit friction. Meanwhile, Bosch reinforced its 7.25-inch steel blade with manganese, an element that slightly raises the metal’s melting point so that it won’t warp and wobble during long cutting sessions.
Bosch Daredevil Framing Blade: $10

THE TEST

We tested the blades on the same 15-amp heavy-duty circular saw. First we made 71 eight-foot cuts through a 2.5-inch-thick stack of plywood with each blade. After neither one so much as flinched, we pushed them through two layers of asphalt shingles sandwiched between two-inch-thick pressure-treated boards interlaced with 15-gauge nails.

THE RESULTS

The Bosch blade was harder to hold steady than the DeWalt, making it difficult to follow the cut line or guide it back if it wandered off. As for staying power, after chewing through three football fields’ worth of plywood, the DeWalt made it through another 54 feet of shingle sandwich before getting stuck; the Bosch quit after 30 feet.

WINNER: DeWalt Precision Framing Blade

Chinese Rare Earth Company Strokes Mustache, Cuts Off World's Access to Rare Earths to Inflate Prices

By Dan Nosowitz

Rare-Earths China produces the vast majority of the world's rare-earth oxides. Wikimedia Commons

China may only have 30 percent of the rare earth in the world, but they essentially have a monopoly--which the rest of the world has been tirelessly trying to work around. (To wit: Japan looks to Vietnam, the U.S. looks to California and Missouri, everyone looks under the sea.) In a slightly devilish business move, China sought to tighten their grip and raise prices by eliminating all sales to its major buyers, the U.S., Japan, and Europe, for one month.

During the sales freeze, China is also consolidating its various rare earths businesses and buying more rare earths. At the moment, about 60 percent of the country's rare earths supply is controlled by a single company, called Inner Mongolia Baotou Steel Rare-Earth. That company is artificially created and listed as a state-owned company, as China has already forced some 35 local companies to either absorb into Inner Mongolia Baotou Steel Rare-Earth, or fade away.

Analysts, according to the AP, think the plan will probably work; rare earths prices have been sliding downward lately, a trend China would certainly like to reverse, and it'll also give the country an opportunity to work on its locally-produced rare earths magnet industry--a much more profitable enterprise than simply selling raw materials. Of course, it's not going to do much to discourage, you know, every other country on the planet from trying to find an alternative to buying rare earths from China.

[AP via DailyTech]

Om jai jagadessh hare -- Shirdi Sai Baba Aarathi

Electrical machines:

An Electrical machine is the generic name for a device that converts mechanical energy to electrical energy, converts electrical energy to mechanical energy, or changes alternating current from one voltage level to a different voltage level.

Electrical machines as employed in industry fall into three categories according to how they convert energy. Generators convert mechanical energy to electrical energy. Motors convert electrical energy to mechanical energy. Transformers change the voltage of alternating current.

Generator

An electric generator is a device that converts mechanical energy to electrical energy. A generator forces electrons to flow through an external electrical circuit. It is somewhat analogous to a water pump, which creates a flow of water but does not create the water inside. The source of mechanical energy, the prime mover, may be a reciprocating or turbine steam engine, water falling through a turbine or waterwheel, an internal combustion engine, a wind turbine, a hand crank, compressed air or any other source of mechanical energy.

There are two main parts of a generator which can be described in either mechanical or electrical terms. In mechanical terms the rotor is the rotating part of an electrical machine, and the stator is the stationary part of an electrical machine. In electrical terms the armature is the power-producing component of an electrical machine and the field is the magnetic field component of an electrical machine. The armature can be on either the rotor or the stator. The magnetic field can be provided by either electromagnets or permanent magnets mounted on either the rotor or the stator. Generators are classified into two types, AC generators and DC generators.

AC generator

An AC generator converts mechanical energy into alternating current electricity. Because power transferred into the field circuit is much less than power transferred into the armature circuit, AC generators nearly always have the field winding on the rotor and the armature winding on the stator.

AC generators are classified into several types. The first is asynchronous or induction generators, in which stator flux induces currents in the rotor. The prime mover then drives the rotor above the synchronous speed, causing the opposing rotor flux to cut the stator coils producing active current in the stator coils, thus sending power back to the electrical grid. The second type is synchronous generators or alternator, in which the current for the magnetic field is provided by a separate DC current source.

DC generator

A DC generator produces direct current electrical power from mechanical energy. A DC generator can operate at any speed within mechanical limits and always output a direct current waveform. Direct current generators known as dynamos work on exactly the same principles as alternators, but have a commutator on the rotating shaft which converts the alternating current produced by the armature to direct current.

Motor

An electric motor converts electrical energy into mechanical energy. The reverse process of electrical generators, most electric motors operate through interacting magnetic fields and current-carrying conductors to generate rotational force. Motors and generators have many similarities and many types of electric motors can be run as generators, and vice versa.

Electric motors are found in applications as diverse as industrial fans, blowers and pumps, machine tools, household appliances, power tools, and disk drives. They may be powered by direct current or by alternating current which leads to the two main classifications: AC motors and DC motors.

AC motor

An AC motor converts alternating current into mechanical energy. It commonly consists of two basic parts, an outside stationary stator having coils supplied with alternating current to produce a rotating magnetic field, and an inside rotor attached to the output shaft that is given a torque by the rotating field.

There are two main types of AC motors, depending on the type of rotor used. The first type is the induction motor, which only runs slightly slower or faster than the supply frequency. The magnetic field on the rotor of this motor is created by an induced current. The second type is the synchronous motor, which does not rely on induction and as a result, can rotate exactly at the supply frequency or a sub-multiple of the supply frequency. The magnetic field on the rotor is either generated by current delivered through slip rings or by a permanent magnet.

DC motor

The brushed DC electric motor generates torque directly from DC power supplied to the motor by using internal commutation, stationary permanent magnets, and rotating electrical magnets. Brushes and springs carry the electric current from the commutator to the spinning wire windings of the rotor inside the motor. Brushless DC motors use a rotating permanent magnet in the rotor, and stationary electrical magnets on the motor housing. A motor controller converts DC to AC. This design is simpler than that of brushed motors because it eliminates the complication of transferring power from outside the motor to the spinning rotor.

An example of a brushless, synchronous DC motor is a stepper motor which can divide a full rotation into a large number of steps. The motor's position can be controlled precisely without any feedback mechanism as long as the motor is carefully sized to the application.

Transformer

A transformer is a static device that converts alternating current from one voltage level to another level (higher or lower), or to the same level, without changing the frequency. A transformer transfers electrical energy from one circuit to another through inductively coupled conductors—the transformer's coils. A varying electric current in the first or primary winding creates a varying magnetic flux in the transformer's core and thus a varying magnetic field through the secondary winding. This varying magnetic field induces a varying electromotive force (EMF) or "voltage" in the secondary winding. This effect is called mutual induction.

 

Induction motor:

An induction motor or asynchronous motor is a type of alternating current motor where power is supplied to the rotor by means of electromagnetic induction.

An electric motor converts electrical power to mechanical power in its rotor (rotating part). There are several ways to supply power to the rotor. In a DC motor, this power is supplied to the armature directly from a DC source while, in an induction motor, this power is induced in the rotating device. An induction motor is sometimes called a rotating transformer because the stator (stationary part) is essentially the primary side of the transformer and the rotor (rotating part) is the secondary side. Unlike the normal transformer which changes the current by using time varying flux, induction motors use rotating magnetic fields to transform the voltage. 

The current in the primary side creates an electromagnetic field which interacts with the electromagnetic field of the secondary side to produce a resultant torque, thereby transforming the electrical energy into mechanical energy. Induction motors are widely used, especially polyphase induction motors, which are frequently used in industrial drives.

Posted by V.Nadarajan