29.09.2008

Культуры клеток в 22х измерениях скоро станут реальностью! :)

Какая прелесть! Это ведь именно то, что нужно сейчас нашим культуральщикам! Трёхмерная культура клеток!!! Это, конечно, не 22 и даже не 11 измерений, но нет ничего невозможного... Информация с http://www.biology-blog.com/blogs/permalinks/9-2008/reversible-3-d-cell-culture-gel-invented.html
Reversible 3-D cell culture gel invented

Reversible 3-D cell culture gel invented
Singapore's Institute of Bioengineering and Nanotechnology (IBN), which celebrates its fifth anniversary this year, has invented a unique user-friendly gel that can liquefy on demand, with the potential to revolutionize three-dimensional (3D) cell culture for medical research.

As reported in Nature Nanotechnology (Y.S. Pek, A. C. A. Wan, A. Shekaran, L. Zhuo and J. Y. Ying, "A Thixotropic Nanocomposite Gel for Three-Dimensional Cell Culture"), IBN's novel gel media has the unique ability to liquefy when it is subjected to a moderate shear force and rapidly resolidifies into a gel within one minute upon removal of the force. This phenomenon of reverting between a gel and a liquid state is known as thixotropy.

IBN's thixotropic gel is synthesized from a nanocomposite of silica and polyethylene glycol (PEG) under room temperature, without special storage conditions. This novel material facilitates the safe and convenient culture of cells in 3D since cells can be easily added to the gel matrix without any chemical processes.

As per IBN Executive Director Jackie Y. Ying, Ph.D., "Cell culture is conventionally performed on a flat surface such as glass slides. It is an essential process in biological and medical research, and is widely used to process cells, synthesize biologics and develop therapys for a large variety of diseases.

"Cell culture within a 3D matrix would better mimic the actual conditions in the body as in comparison to the conventional 2D cell culture on flat surfaces. 3D cell culture also promises the development of better cell assays for drug screening," Dr. Ying added.

Another key feature of IBN's gel is the ease with which scientists can transfer the cultured cells from the matrix by pipetting the mandatory amount from the liquefied gel.

Unlike conventional cell culture, trypsin is not mandatory to detach the cultured cells from the solid media. As trypsin is an enzyme that is known to damage cells, particularly in stem cell.

cultures, the long-term quality and viability of cells cultured using IBN's thixotropic gel would improve substantially without the exposure to this enzyme.

Scientists are also able to control the gel's stiffness, thus facilitating the differentiation of stem cells into specific cell types.

"Ways to control stem cell differentiation are important as stem cells can be differentiated into various cell types. Our gel can provide a novel method of studying stem cell differentiation, as well as an effective new means of introducing biological signals to cells to investigate their effect in 3D cultures," said Shona Pek, IBN Research Officer.

Andrew Wan, Ph.D., IBN Team Leader and Principal Research Scientist, added, "Another interesting property of the gel is its ability to support the extracellular matrix (ECM) secretions of cells. Gel stiffness is modulated by ECM secretions, and can be used to study ECM production by cells responding to drug therapys or disease conditions.

"The thixotropic gel may then provide new insights for basic research and drug development," Dr. Wan added.


Posted by: Janet http://www.a-star.edu.sg/astar/index.jsp

21.09.2008

Жир жиру рознь!

Жировые клетки людей с лишним весом отличаются от таковых у стройных товарищей. Об этом - статья на http://www.scientificblogging.com/news_releases/fat_in_fat_people_different_than_fat_in_thin_people

Fat In Fat People Different Than Fat In Thin People
Submitted by News Staff on 27 August 2008 - 12:30am. Microbiology

Not all fat is created equal, it seems. A Temple University study finds fat in obese patients is "sick" when compared to fat in lean patients.

Why 'sick? When our bodies don't work properly, we say we're sick. The study in the September issue of Diabetes finds that the same could be said for fat tissue found in obese patients. The cells in their fat tissue aren't working properly and as a result, are sicker than cells found in lean patients' fat tissue.

Lead author Guenther Boden, M.D. theorizes that "sick fat" could more fully explain the link between obesity and higher risk of diabetes, heart disease and stroke.

Researchers from the departments of endocrinology, biochemistry and surgery at the Temple University School of Medicine took fat biopsies from the upper thighs of six lean and six obese patients and found significant differences at the cellular level.

"The fat cells we found in our obese patients were deficient in several areas," said Boden, Laura H. Carnell Professor of Medicine and chief of endocrinology. "They showed significant stress on the endoplasmic reticulum, and the tissue itself was more inflamed than in our lean patients."

Endoplasmic reticulum (ER) is found in every cell and helps synthesize proteins and monitor how they're folded. The stress that Boden describes causes the ER in fat cells to produce several proteins that ultimately lead to insulin resistance, which has been found to play a major role in the development and progression of obesity-related conditions.

The National Institutes of Health recently reported that each time a body mass index (BMI) over 25 is raised by one point, the risk for diabetes increases 25 percent and the risk for heart disease increases 10 percent.

Reducing weight can help reduce stress on the ER, which can lower the risk of insulin resistance and the resulting conditions. Currently Boden and his team are looking at whether free fatty acids are a potential cause for this ER stress.

Other authors on this study include Xunbao Duan, Carol Homko, Ezequiel J. Molina, WeiWei Song, Oscar Perez, Peter Cheung and Salim Merali of Temple University School of Medicine. Funding for this research was provided by grants from the National Institutes of Heath, the Groff Foundation and a mentor-based training grant from the American Diabetes Association.

Новые лекарства от шизофрении!

Ангельская пыль может быть очень полезна... для исследований. Прочитала на http://blog.wired.com/wiredscience/2008/09/four-experiment.html
Angel Dust Inspired a New Schizophrenia Drug
By Aaron Rowe EmailSeptember 15, 2008 | 11:32:36 PMCategories: Big Pharma, Chem Lab, Chemistry, Medicinal Chemistry, Psychiatry

Pcp

When scientists learned that PCP, also known as angel dust, can cause every single symptom of schizophrenia, they wondered if chemicals that have the opposite effect could fight mental disorders. That insight led to them to discover a new class of antipsychotic medications.

To understand how the recreational drug plays tricks on the mind, neuroscientists gave it to lab rats. Those researchers could counteract the strange behavior of their furry assistants by stimulating brain proteins called glutamate receptors. Big drug companies, including Eli Lilly, took note of that discovery and started searching for molecules that can push the same psychological buttons in humans.

In the Sept. 15 issue of Chemical and Engineering News, Carmen Drahl told that story, along with the tales of three other experimental medications that could turn the tide against schizophrenia. Each compound operates in a completely different way, and all of them have been tested on human volunteers.

That is really big news because doctors have been stuck using the same class of pills -- dopamine blockers -- since the 1950's.

Drahl got the scoop on the new treatments during a special seminar about schizophrenia, which took place last month during the American Chemical Society meeting in Philadelphia.

LY404039 was discovered by Eli Lilly and works by activating glutamate receptors. It is furthest along in the approval process. Unlike other schizophrenia drugs, it does not cause excessive weight gain.
DCCCyB was developed by Merck, and it does the job by blocking glycine transporters
PF-2545920 was tested by Pfizer, and it gums up a phosphodiesterase enzyme.
TC-5619 was invented at Targacept and it excites nicotine receptors with far more precision than the finest cigarettes. Schizophrenics tend to medicate themselves by smoking, and new drugs may offer them a similar kind of relief without the serious health risks that come from tobacco products.

If these drugs are approved by the FDA, the social implications could be profound: A great deal of homelessness is caused by psychological problems. Perhaps some of these new substances will allow people with serious mental illness to become functional and live somewhat normal lives.

18.09.2008

68 ключевых молекул!

68 - ЭТО ПОЧТИ 69 :) Читаем!

http://www.scientificblogging.com/news_releases/68_molecules_may_hold_the_key_to_understanding_disease

68 Molecules May Hold the Key to Understanding Disease
Submitted by News Staff on 4 September 2008 - 12:00am. Microbiology

Why is it that the origins of many serious diseases remain a mystery? In considering that question, a scientist at the University of California, San Diego School of Medicine has come up with a unified molecular view of the indivisible unit of life, the cell, which may provide an answer.

Reviewing findings from multiple disciplines, Jamey Marth, Ph.D., UC San Diego Professor of Cellular and Molecular Medicine and Investigator with the Howard Hughes Medical Institute, realized that only 68 molecular building blocks are used to construct these four fundamental components of cells: the nucleic acids (DNA and RNA), proteins, glycans and lipids. His work, which illustrates the primary composition of all cells, is published in the September issue of Nature Cell Biology.

Like the periodic table of elements, first published in 1869 by Russian chemist Dmitri Mendeleev, is to chemistry, Marth’s visual metaphor offers a new framework for biologists.

Illustration of "molecular building blocks."

This new illustration defines the basic molecular building blocks of life and currently includes 32 glycans (sugar linkages found throughout the cell) and eight kinds of lipids (which compose cell membranes) along with the more well-known 20 amino acids that are used to make proteins and the eight nucleosides that compose the nucleic acids, DNA and RNA.

“These 68 building blocks provide the structural basis for the molecular choreography that constitutes the entire life of a cell,” said Marth. “And two of the four cellular components are produced by these molecular building blocks in processes that cannot be encoded by the genes. These cellular components – the glycans and lipids – may now hold the keys to uncovering the origins of many grievous diseases that continue to evade understanding.”

Currently, the vast majority of medical research looks to the human genome and proteome for answers, but those answers remain elusive, and perhaps for good reason.

“We have now found instances where the pathogenesis of widespread and chronic diseases can be attributed to a change in the glycome, for example, in the absence of definable changes in the genome or proteome,” Marth said, adding that, as biomedical researchers, “we need to begin to cultivate the integration of disciplines in a holistic and rigorous way in order to perceive and most effectively manipulate the biological mechanisms of health and disease.”

“What is important is that no one has composed it and laid it out so clearly before,” said Ajit Varki, M.D., Distinguished Professor of Medicine and Cellular and Molecular Medicine and founder and co-director of the Glycobiology Research and Training Center at UC San Diego School of Medicine, and chief editor of the major textbook in the field, The Essentials of Glycobiology. “Glycobiology, for example, is a relatively new field of study in which researchers at UC San Diego have much expertise, and Dr. Marth’s work further illustrates the importance of these glycan molecules.”

Marth believes that biology should become more integrative both in academic and research settings. “I’m one who believes that we don’t need to sacrifice breadth of knowledge in order to acquire depth of understanding.”

04.09.2008

Начало всех начал :))) Стволовая клетка-мама.

Мама крови. Вот она! Наконец, эмбриональная предшественница клеток крови - чётко определена. Информация с http://www.scientificblogging.com/news_releases/discovery_mother_of_all_blood_stem_cells
Discovery - 'Mother' Of All Blood Stem Cells

Submitted by News Staff on 29 August 2008 - 1:00am. Developmental
Johns Hopkins researchers say they have discovered the earliest form of human blood stem cells and deciphered the mechanism by which these embryonic stem cells replicate and grow. They also found a surprising biological marker that pinpoints these stem cells, which serve as the progenitors for red blood cells and lymphocytes.

The research reported today used federally approved embryonic stem cell lines.

The biochemical marker, angiotensin-converting enzyme (ACE), is well known for its role in the regulation of blood pressure, blood vessel growth, and inflammation. ACE inhibitors are already widely used to treat hypertension and congestive heart failure, and the findings are, the researchers say, likely to hold promise for developing new treatments for heart diseases, anemias, leukemia and other blood cancers, and autoimmune diseases because they show for the first time that ACE plays a fundamental role in the very early growth and development of human blood cells.

"We figured out how to get the 'mother' of all blood stem cells with the right culture conditions," says Elias Zambidis, M.D., Ph.D., of the Institute of Cell Engineering at the Johns Hopkins University School of Medicine and the Division of Pediatric Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

"There is real hope that in the future we can grow billions of blood cells at will to treat blood-related disorders, and just as critically if not more so, we've got ACE as a 'new' old marker to guide our work," Zambidis adds.

Researchers did not expect ACE to have a role in blood stem cells, he notes, "but were very pleasantly surprised to discover it as a beacon for finding the earliest blood stem cells known, as well as new ways to find and manipulate this marker to make them grow."

The team's findings, published Aug. 26 in the online edition of the journal Blood, explain that these earliest stem cells marked by ACE, called hemangioblasts, first arise normally in the developing human fetus, when a woman is three or four weeks pregnant. Hemangioblasts can now be derived in unlimited supply experimentally from cultured human embryonic stem cells, which are the origin of all cell types in the body. These hemangioblasts go on to become either blood cells or endothelial cells, which form the inner lining of the heart, veins and arteries, and lymph vessels.

The research grew out of Zambidis' interest in understanding the complex biological processes of blood development and the transformation of embryonic stem cells into the various types of cells that make up the human body.

Hemangioblasts make the body's earliest form of blood in the fetal yolk sac, which nourishes a fertilized egg, and later in the fetal liver and bone marrow. However, because human embryonic cells disappear early in gestation, their role in the early production of blood could not, to the researchers' knowledge, be studied in humans because scientists had no way to identify these human progenitor blood stems cells to follow their development. The scientists suspected they existed in humans, however, because they have been found in mice and zebra fish.

To find the blood stem cell, Zambidis' team grew human embryonic stem cells in culture and fed them growth factors over 20 days. Each time the cell colonies expanded, the researchers sampled individual cells, searching for ones capable of making both endothelial and blood cells, the hallmark of hemangioblasts.

They plucked the newly discovered hemangioblasts from culture dishes, grew them in conditions that Zambidis and his team developed to speed replication, and tested cells for their ability to make endothelial and blood cells. Cells capable of making endothelial cells and all the elements of blood (platelets, and white and red cells) were specifically marked with ACE on their outer surface.

The researchers found not only that ACE was a marker for hemangioblasts, but turning off the enzyme also helps guide the cells' replication and maturation into either blood or endothelial cells. By treating the hemangioblasts with losartan, an ACE pathway blocking agent routinely used to treat high blood pressure, dramatically increased the rate of blood cell production.

The next step, Zambidis adds, is to test this research in animal models and show that "we can make lots and lots of blood cells from human stem cells for transfusions, regenerate new vascular trees for heart diseases, as well as create test tube factories for making transplantable blood cells that treat diseases. We are very far from treatment," Zambidis cautions, "but this is a big step."

If the new technique of mass producing progenitor blood cells is eventually proven to work in humans, it would allow patients getting bone marrow transplants to have their own stem cells creating the blood they need, significantly reducing rejection risk.

The research reported today used federally approved embryonic stem cell lines, but other related research by the team comes from nonapproved lines. The study was supported by grants from the National Institutes of Health and the Maryland Stem Cell Research Fund.

Загадка клеточного деления - разгадана!

Ну разве не радость? Прочитала на http://www.scientificblogging.com/news_releases/50_year_cell_division_mystery_solved_say_researchers

Researchers from Oregon State University say they have resolved a controversy that cellular biologists have been arguing over for nearly 50 years, with findings that may aid research on everything from birth defects and genetic diseases to the most classic "cell division" issue of them all – cancer.

The exact mechanism that controls how chromosomes in a cell replicate and then divide into two cells, a process fundamental to life, has never been completely pinned down, researchers say. You can find the basics in any high school biology textbook, but the devil is in the details.

"Researchers have been debating cell cleavage ever since the cell was discovered, with two basic models proposed around 1960 of how a contractile ring pulls together and allows a single cell to split into two," said Dahong Zhang, an OSU associate professor of zoology. "Part of the problem is that until now there was no decisive way to manipulate the cytoskeleton, such as the microtubules and filaments that are involved, and see what was happening as it occurred."

To address that, Zhang developed some new instrumentation that uses "microneedles" and state-of-the-art imaging techniques which allow direct manipulation of the cytoskeleton, while capturing the results of contractile ring formation. The system has not only solved this decades-old riddle, but "the technology is a very powerful new approach," Zhang said, that should find applications in other cell biology research issues.

It has been known for some time, scientists say, that a "contractile ring," which is composed of some of the same fibers used in muscle contraction, move into the correct position, pull and split a cell in two after its chromosomes have been separated. This is distribution of genetic materials at its most basic level, and it has to be done at exactly the right place and time. When the process breaks down, cancer and other serious medical or genetic issues can be a result.

But if you think of the cell as a sphere, what was less clear was whether the "equator" contracted or the "poles" relaxed to allow this contraction and division. Two distinct theories were formed, called polar relaxation and equatorial stimulation, to explain this aspect of cell division – and some scientists have spent much of their careers arguing for one side or the other.

Turns out, Zhang said, that both sides were correct. Nature and evolution have actually created a basic way for a cell to divide with a backup system that can work if the other approach fails.

"Accurate cell division is one of the most critical of all life functions, and there clearly is an evolutionary value to having redundancy, a system able to do it two different ways," Zhang said. "It makes perfect sense when you think about it. The findings speak plainly for themselves, and there should no longer be a question over which model is right."

By labeling cells and moving microtubules around while still being able to see them and their impact on microfilaments, OSU researchers were able to selectively inhibit one mechanism of cell division or the other. They discovered that in the same cell type, it could divide either by polar relaxation or equatorial stimulation – the two mechanisms are not mutually exclusive.

The findings, Zhang said, add significantly to the basic understanding of cell biology, and should be of special interest to cancer researchers. Cancer is essentially the loss of normal control over cell division and migration. In fact, a compound used in Zhang's laboratory to inhibit cell division while they studied it was taxol – a commonly used cancer drug.

Accurate and effective cell division, researchers say, is also key to the understanding of some genetic diseases, miscarriages, birth defects and other issues.

The studies were supported by the National Science Foundation and the American Heart Association.

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