Inner workings of virus responsible for rare skin cancer

Posted by BiomechanismScientists at the University of Pittsburgh Cancer Institute have begun to uncover how the virus that causes most Merkel cell carcinoma – a rare and aggressive skin cancer – operates, meaning that a rational chemotherapeutic target for this cancer could be developed in the near future.

Patrick Moore, M.D., M.P.H., an American Cancer Society professor in the laboratory of Yuan Chang and Patrick Moore at the University of Pittsburgh Cancer Institute in Pittsburgh, Pa., presented these study results at the Second AACR International Conference on Frontiers in Basic Cancer Research, held here Sept. 14-18, 2011.

Anatomy of the skin, showing the epidermis, dermis, and subcutaneous tissue.

Merkel cell carcinoma is a rare and highly aggressive cancer, the incidence of which has increased fourfold during the last 20 years, particularly in immunosuppressed populations, according to Moore.

“Unfortunately, Merkel cell carcinoma is difficult to treat and clinical trials of chemotherapeutics have been disappointing in affecting clinical course and survival,” he said. “Discovery of the molecular cause for this cancer provides opportunities to directly target the cellular pathways that are perturbed by the virus.”

In 2008, Moore and colleagues discovered Merkel cell polyomavirus (MCV), the virus that causes most Merkel cell carcinoma. Polyoma refers to the ability of some members of this family to produce multiple tumors in animal models. Their laboratory previously discovered the herpes virus that causes Kaposi’s sarcoma, cancer that commonly occurs in patients with AIDS.

“MCV is the first polyomavirus to be consistently associated with human cancer, and is believed to cause 80 percent of Merkel cell carcinoma,” Moore said.

MCV is a natural component of the human skin and is usually harmless, according to Moore. In fact, most adults carry the virus in some part of their skin cells. However, if someone becomes immunodeficient and the virus undergoes specific mutations, then it can generate Merkel cell carcinoma.

In the three years since they discovered MCV, this group has also discovered several of the unique characteristics of the virus. Most recently, their studies showed that MCV small T antigen protein is a new oncogene that can contribute to abnormal cell growth in both rodent and human cells. In addition, MCV does not act the same as other polyomaviruses that have served as classic models of cancer. These other polyomaviruses depend on viral interaction with the enzyme PP2A and heat-shock proteins; MCV interacts with them, but does not depend on them.

Moore and colleagues found that MCV could still cause the abnormal cell growth even after abolishing PP2A and heat-shock protein binding sites. The researchers hope to develop treatments that will directly target the cellular pathways affected by this virus.

“We are making headway on this approach now and have tested more than 1,350 drugs to identify better methods to treat this virus-caused cancer,” Moore said.

Targeting cholesterol to fight deadly brain cancers

Blocking the uptake of large amounts of cholesterol into brain cancer cells could provide a new strategy to battle glioblastoma, one of the most deadly malignancies, researchers at UCLA’s Jonsson Comprehensive Cancer Center have found.

Posted by Biomechanism 

Brain tumor

The study, done in cells lines, mouse models and analysis of tissue from brain cancer patients, uncovered a novel mechanism by which the most commonly activated oncogene, the mutated epidermal growth factor receptor (EGFR), overcomes normal cell regulatory mechanisms to feed large amounts of cholesterol to the brain cancer cells, said Dr. Paul Mischel, a professor of pathology and laboratory medicine and molecular and medical pharmacology, a Jonsson Cancer Center researcher and senior author of the study.

The study appears Sept. 15 in Cancer Discovery, the newest peer-reviewed journal of the American Association for Cancer Research. It shows that EGFRvIII, common in glioblastoma, promotes the import of cholesterol into cancer cells by up-regulating its cellular receptor, the LDL receptor, promoting rapid tumor growth and survival.

There are at least three ways by which cells normally tightly control their cholesterol levels – synthesis, import and efflux, or pumping out the cholesterol, Mischel said.

“Our study found that the mutant EGFR hijacks this system, enabling cancer cells to import large amounts of cholesterol through the LDL receptor,” Mischel said. “This study identifies the LDL receptor as a key regulator of cancer cell growth and survival, and as a potential drug target.”

Mischel and his colleagues hypothesized that targeting the LDL receptor for destruction could result in strong anti-tumor activity against glioblastoma. They showed that a drug that activates the nuclear Liver X Receptor, a critical regulator of intracellular cholesterol that ensures appropriately balanced levels, degraded the LDL receptor in tumor cells bearing EGFR mutations, potently killing the cancerous tumors in mice.

About 45 percent of glioblastoma patients have cancers driven by mutated EGFR, so the findings have the potential to help almost half of those diagnosed with this aggressive malignancy. EGFR also is mutated in a number of other cancers, indicating that these findings may have relevance for other malignancies.

“This study suggests a potential therapeutic strategy to treat glioblastoma, and potentially a broader range of cancer types,” Mischel said.

In a previous study, Mischel showed that inhibiting fatty acid synthesis in brain cancer cells may offer an additional option to treat those with mutated EGFR. Rapidly dividing cancer cells also require these fatty acids to form new membranes and provide energy for the cells. Mischel and his team found the same cell signaling pathway is at work in fatty acid synthesis and the import of cholesterol into cancer cells.

“That was a surprise here, this ghastly trick of the cancer cells,” Mischel said. “The same mutation is coordinately regulating both the cholesterol and fatty acid synthesis mechanisms.”

Going forward, Mischel and his colleagues will do more preclinical studies that could lead to clinical trials of drugs that activate the Liver X receptor.

Glioblastoma is the most common brain malignancy and one of the most lethal of all cancers, killing most of those diagnosed within 12 to 15 months despite aggressive treatment. It is also one of the most chemotherapy- and radiation-resistant cancers. New treatments are desperately needed, Mischel said.

“This study uncovers a novel and potentially therapeutically targetable tumor cell growth and survival pathway, which could result in more effective treatments for patients,” he said.

Mischel’s findings are the result of a collaboration with Dr. Peter Tontonoz, a Howard Hughes Medical Institute investigator and a professor of pathology and laboratory medicine at UCLA, Dr. Timothy Cloughesy, professor of neurology and director of neuro oncology at UCLA’s Jonsson Comprehensive Cancer Center, and Dr. Deliang Guo, an assistant professor of radiation oncology at the Ohio State University Comprehensive Cancer Center.

Researchers discover a switch that controls stem cell pluripotency

Posted by Biomechanism 
Scientists have found a control switch that regulates stem cell “pluripotency,” the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.

Induced pluripotent stem cells (iPSCs) are a novel class of stem cells that can turn into any cell type in the body, similar to embryonic stem cells. Unlike embryonic stem cells, these cells do not require the controversial step of isolating cells from a developing blastocyst.

Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in “adult” cells—those that had become the specialized cells that comprise organs and perform functions.

“It opens the field to the fact that alternative splicing plays a really important role in stem cell pluripotency,” said Prof. Benjamin Blencowe, principal investigator on the study and a Professor in the University of Toronto’s Departments of Molecular Genetics and Banting and Best Department of Medical Research. “We’re beginning to see an entirely new landscape of regulation, which will be crucial to our understanding of how to produce more effective pluripotent stem cells for therapeutic and research applications.”

The findings were published in the current online edition of the scientific journal Cell.

Alternative splicing works by allowing different segments of genetic messages, also known as messenger RNAs, to be spliced in different combinations as the messages are copied from a gene’s DNA. Those combinations make different messenger RNAs, which in turn become different proteins.

In stem cells, scientists have shown that a core set of proteins called transcription factors control pluripotency.

The splicing event discovered by Blencowe’s team, including first author on the study Dr. Mathieu Gabut, changes the DNA binding properties of FOXP1 in a way that then controls the expression of the core pluripotency transcription factors, to facilitate maintenance of pluripotency. “As a mechanism that controls those core transcription factors, it’s right at the heart of the regulatory process of pluripotency,” said Blencowe.

At the same time, the mechanism represses the genes required for differentiation—the process whereby by a stem cell loses “stemness” and becomes a specific cell type that makes up an organ or performs a function.

As well, in collaboration with colleagues including Profs. Jeff Wrana and Andras Nagy in the Samuel Lunenfeld Research Institute at Mount Sinai Hospital, also Professors in U of T’s Department of Molecular Genetics, the splicing switch identified by Blencowe’s team was shown to play a role in “reprogramming,” a potentially therapeutic technique in which researchers coax adult cells back into induced pluripotent stem cells by introducing the core transcription factors. “That’s an important area in the field where we need better understanding because reprogramming, especially with human cells, is very inefficient,” said Blencowe. “Often when reprogrammed stem cells are not fully reprogrammed they become tumorigenic and can lead to cancer.”

Potential applications for stem-cell science include growing cells and tissues to test new drugs or to repair or replace damaged tissues in many diseases and conditions, including heart disease, diabetes, spinal cord injury and Alzheimer’s disease.

As well, a better understanding of the mechanisms that regulate pluripotency, cell division and differentiation will provide knowledge of how diseases like cancer arise and suggest more targeted therapeutic approaches.

Blencowe and his lab have recently turned their attention to what might be controlling the factors that control both alternative splicing and the maintenance of stem-cell pluripotency. They have, said Blencowe, a few tantalizing glimpses. “There’s still a lot to figure out, but I personally believe there is huge potential in the future. If we can fully understand the regulatory controls that allow us to make uniform populations of fully reprogrammed stem cells, there’s no reason why they shouldn’t be effective for many different therapies. It will come.”

A Personal Turbine Makes Your Rooftop Into a Wind Farm

By Sarah Parsons

Among homeowners, wind energy has never caught on, in large part because personal turbines are often noisy and inefficient. Most turbines need strong winds to turn a heavy central generator and create current, a design with two main disadvantages. First, the gears make a lot of noise. Plus, the generator is positioned at the blades’ center, which moves at one tenth the speed of the periphery. And less speed translates to less power.

Honeywell’s wheel-shaped WT6500 takes an entirely new approach. Magnets mounted near the tips of its 20 blades sweep through an outer ring of copper coils to produce a current, making the entire wheel the generator. Because this arrangement traps energy from the fast-moving blade tips and eliminates the heavy central generator, the WT6500 can pull a current from winds as slow as two miles an hour (most home turbines need 8mph gusts). Better suited to home use than other turbine designs, the wheel is six feet in diameter, whisper-quiet, and can produce up to 1,500 kilowatt-hours of power per year—enough to replace about 15 percent of an average household’s energy bill. Depending on an area’s clean-energy incentives, the turbine can pay for itself in only a couple of years, though most owners will make back their investment in five to 10.

HOW IT WORKS

• A flap on either side of the wheel catches wind, which spins the turbine toward the gusts.
• The wind moves the turbine wheel, including its 20 blades.
• The blade tips contain rare-earth metal magnets. As they sweep through copper coils in the outer frame, they generate a DC current.
• An inverter [not shown] gathers the current. It can store the power in a battery or convert it to AC for immediate use.

New class of stem cell-like cells discovered offers possibility for spinal cord repair

“Collaborative study using Allen Spinal Cord Atlas finds previously overlooked cell type with implications for treating spinal cord injury and disease.”

Posted by Biomechanism 

The Allen Institute for Brain Science announced today the discovery of a new class of cells in the spinal cord that act like neural stem cells, offering a fresh avenue in the search for therapies to treat spinal cord injury and disease. The published collaborative study, authored by scientists from the University of British Columbia, the Allen Institute for Brain Science and The Montreal Neurological Institute and Hospital at McGill University and titled “Adult Spinal Cord Radial Glia Display a Unique Progenitor Phenotype,” appears in the open access journal PLoS One.

Spinal cord injury (SCI) is damage to the nerves within the spinal canal, thereby affecting the spinal cord's ability to send and receive messages from the brain to the body's systems that control sensory, motor and autonomic function below the level of injury.

The research team utilized the Allen Spinal Cord Atlas, a finely detailed genome-wide map of gene expression throughout the mouse spinal cord, to compare the genes expressed, or turned on, in adult spinal cord radial glia with those found in other neural stem cells, revealing a signature set of 122 genes that indicate the likeness of these cells to classic neural stem cells.

The nervous system has historically been thought to be incapable of repairing itself, as the cells used to create it are exhausted during development. With the identification of these new stem cell-like radial glial cells, it may be possible to activate a certain set of genes in order to encourage those cells to reconstruct a damaged network in the adult spinal cord.

“By using the Allen Spinal Cord Atlas, we were able to discover a brand new cell type that has previously been overlooked and that could be an important player in all manner of spinal cord injury and disease, including multiple sclerosis and ALS,” said Jane Roskams, Ph.D., neuroscientist at the University of British Columbia and senior author of the study.

From disabled veterans to those afflicted with Lou Gehrig’s disease (ALS) or Spinal Muscular Atrophy, spinal cord related diseases and disorders affect people of all ages including nearly one-quarter of a million Americans who have suffered from a spinal cord injury; as many as 30,000 Americans who suffer from ALS at any given time; and approximately 2.5 million people worldwide who suffer from multiple sclerosis.

“This is a tremendous example of how our public atlas resources can lead to critical discoveries that offer promising avenues for developing much needed new clinical therapies,” said Allan Jones, Ph.D., Chief Executive Officer of the Allen Institute.

Dr. Roskams, who led the collaborative research team, has said that it is possible this pool of cells was overlooked because of its unusual location, and because scientists have been working with limited information. With the availability of the public, online Allen Spinal Cord Atlas, the information accessible to researchers has been vastly increased.

In the search for neural stem cells, scientists have been using a few known genes as clues to find candidates deep in the middle of the spinal cord. While some neural stem cells have been discovered there, the newly identified class of spinal cord radial glia run along the edge of the spinal cord, an incredibly convenient location for activating them with minimal secondary damage to help the spinal cord repair during disease or after injury.

“When we first saw known neural stem cell genes appearing in these cells on the edge of the cord, I realized we not only had a brand new cell, but had the capacity to reveal a new gene set that may also guide us to hidden neural stem cells in atypical locations in the brain. I did not expect so many of them to link to human diseases,” Dr. Roskams said.

Identifying these cells and the genes relevant to activate them opens fresh new pathways to explore effective therapies to treat spinal cord injury and several types of neurodegenerative disease.

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Citation 
Petit, A. et al. (2011) Adult Spinal Cord Radial Glia Display a Unique Progenitor Phenotype. PLoS ONE 6(9): e24538. doi:10.1371/journal.pone.0024538

ஒரே குடும்பத்தில் மூன்று ஒரே ராசிக்காரர்கள் இருந்தால் என்ன பரிகாரம் செய்யலாம்?

ஒரே குடும்பத்தில் மூன்று ஒரே ராசிக்கார்கள் இருந்தால் என்ன பரிகாரம் செய்யலாம்?

கணவன்-மனைவி இருவரும் ஏக ராசியாக இருக்கக் கூடாது என்பதால்தான் திருமணத்திற்கு முன்னரே பொருத்தம் (ராசிப் பொருத்தம் உட்பட) பார்த்து மணமுடிக்க வேண்டும் எனக் கூறுகிறோம்.

ஆனால் பெற்றோர் கையை மீறி காதல் திருமணம் உள்ளிட்ட நிகழ்வுகளால் ஏக ராசிப் பொருத்தம் அமைந்து விடுகிறது. அதிலும், அந்த தம்பதிகளுக்கு பிறக்கும் குழந்தையும் அதே ராசியில் பிறந்து விட்டால், ஒரே குடும்பத்தில் 3 பேர் ஏக ராசிக்காரர்களாக அமைந்து விடுகின்றனர்.




இதனால் நல்லதும், கேட்டதும் - ஒரே நிறத்தில் நடக்கும். 

இதன் காரணமாக ஏழரைச் சனி, அஷ்டமச் சனி, மோசமான தசை நடக்கும் போது குடும்பத்தில் உள்ள அனைவரும் ஒரே நேரத்தில் பாதிக்கப்படுவர். அதனால் திடீர் விபத்துகள், இழப்புகள் ஏற்படும்.

ஒரே குடும்பத்தில் 3 பேரும் ஏகராசிக்காரர்களாக அமையும் பட்சத்தில் ஆண்டுதோறும் திருச்செந்தூர் முருகன் கோயிலுக்கு சென்று வழிபடுவதே சிறந்த பரிகாரமாகும்.

ஒரே ராசியில் ஒருவருக்கு மேல் ஒரு குடும்பத்தில் இருந்தால் சம்ஹார ஸ்தலங்களுக்கு (கடலோரமாக உள்ள) சென்று வழிபாடு நடத்தலாம் என பழைய நூல்களில் கூறப்பட்டுள்ளது.

ஏக ராசிக்காரர்களாக இருக்கும்பட்சத்தில் ஏழரைச் சனி, அஷ்டமச் சனி நடந்தால் குடும்பத்தில் இருந்து ஒருவர் தற்காலிகமாக பிரிந்து இருப்பது நல்லது. மகன், மகளை உறவினர்கள் வீட்டில் அல்லது நல்ல விடுதியில் சேர்க்கலாம். கணவன்/மனைவி பணியிட மாற்றம் செய்து கொள்ளலாம். இதனால் விவாதம் மூலம் வரும் பிரச்சனைகளைத் தவிர்க்கலாம்.

ஏழரைச் சனி, அஷ்டமச் சனி நடக்கும் போது , மற்றும் மோசமான தசா , புக்தி காலங்களில் அனைவரும் ஒரே வண்டியில் பயணம் செய்வதையும் தவிர்க்க வேண்டும்.

Read more: http://www.livingextra.com/2011/09/blog-post_16.html#ixzz1YClvLzUK