Sugar helps cancer cells regulate voltage

Sugar helps cancer cells regulate voltage

Sugar helps cancer cells regulate voltage

Researchers in an attempt to understand why Cancers will hold onto sugar yet not use it as fuel discovered that Cancer Cells use sugar as a sort of voltage regulator.

1. Ca2 -dependent demethylation of phosphatase PP2Ac promotes glucose deprivation–induced cell death independently of inhibiting glycolysis. Science Signaling, 2018; 11 (512): eaam7893 DOI: 10.1126/scisignal.aam7893

What you think, feel, and learn has cross-generational effects

Contact: Rhiannon Bugno Biol.Psych@utsouthwestern.edu 214-648-0880 Elsevier

Life experiences put their stamp on the next generation: New insights from epigenetics

A review from Biological Psychiatry

Philadelphia, PA, February 14, 2013 – The 18th century natural philosopher Jean-Baptiste Lamarck proposed that the necks of giraffes lengthened as a consequence of the cumulative effort, across generations, to reach leaves just out of their grasp. This view of evolution was largely abandoned with the advent of modern genetic theories to explain the transmission of most important traits and many medical illnesses across generations.

However, there has long been the impression that major life events, like psychological traumas, not only have effects on individuals who directly experience these events, but also have effects on their children. For example, cross-generational effects have been well-documented in the children of Nazi death camp survivors. Similar issues have been reported in the context of mood disorders and addiction. Until recently, these trans-generational effects were attributed to changes in the way that parents treated their children or the child’s reaction to learning about the parent’s history.

In the most recent issue of Biological Psychiatry, Swiss researchers from the University of Zurich and Swiss Federal Institute of Technology, led by Dr. Isabelle Mansuy, discuss how the emergence of the field of epigenetics has introduced a new component to this discussion – the trans-generational transmission of changes in the regulation of gene expression.

“The question of the inheritance of acquired traits has puzzled biologists and clinicians for decades. Although it has been consistently observed as early as in the 18th century, the time has now come that sufficiently strong and convincing evidence has accumulated to firmly accept it,” said Mansuy.

The genetic transmission of traits reflects alterations in genetic structure, i.e., the base pairs that form DNA. Epigenetics, on the other hand, involves cellular processes that do not alter the structure of DNA. Instead, epigenetic mechanisms, including the methylation of DNA or of specific residues on histone “supporter” proteins, influence the extent to which individual genes are converted into messenger RNA. These changes can occur in any cell of the body, but when they occur in the germ cells (sperm or eggs) the changes may be passed to the next generation.

The changes in DNA structure are random events that acquire functional significance in the context of Darwin’s “natural selection” process. In contrast, the epigenetic reactions to specific environments are designed to enable that organism to cope with that context. When these traits are passed to the next generation, it is as if the newborn arrives prepared for that specific environment. Problems arise when the epigenetic processes give rise to traits that are not adaptive for the offspring, such as heightened stress reactivity, or when the environment has changed.

“This is a remarkable story with far-reaching implications,” commented Dr. John Krystal, Editor of Biological Psychiatry. “There is a suspicion that epigenetic processes may be reversed more easily than genetic traits, exemplified by the development of HDAC inhibitors. This is a rapidly evolving research area that has captured a great deal of attention.”

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The article is “Transgenerational Epigenetic Effects on Brain Functions” by Johannes Bohacek, Katharina Gapp, Bechara J. Saab, and Isabelle M. Mansuy (doi: 10.1016/j.biopsych.2012.08.019). The article appears in Biological Psychiatry, Volume 73, Issue 4 (February 15, 2013), published by Elsevier.

 

Notes for Editors

Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Isabelle Mansuy at +41 44 635 3360 or mansuy@hifo.uzh.ch.

The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 5th out of 129 Psychiatry titles and 16th out of 243 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2011 Impact Factor score for Biological Psychiatry is 8.283.

About Elsevier 

Elsevier is a world-leading provider of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including The Lancet and Cell, and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier’s online solutions include ScienceDirect, Scopus, Reaxys, ClinicalKey and Mosby’s Nursing Suite, which enhance the productivity of science and health professionals, and the SciVal suite and MEDai’s Pinpoint Review, which help research and health care institutions deliver better outcomes more cost-effectively.

A global business headquartered in Amsterdam, Elsevier employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC, a world-leading provider of professional information solutions in the Science, Medical, Legal and Risk and Business sectors, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

New form of cell division found

Contact: Dian Land dj.land@hosp.wisc.edu 608-261-1034 University of Wisconsin-Madison

MADISON — Researchers at the University of Wisconsin Carbone Cancer Center have discovered a new form of cell division in human cells.

They believe it serves as a natural back-up mechanism during faulty cell division, preventing some cells from going down a path that can lead to cancer.

“If we could promote this new form of cell division, which we call klerokinesis, we may be able to prevent some cancers from developing,” says lead researcher Dr. Mark Burkard, an assistant professor of hematology-oncology in the Department of Medicine at the UW School of Medicine and Public Health.

Burkard will present the finding on Dec. 17 at the annual meeting of the American Society for Cell Biology in San Francisco.

A physician-investigator who sees breast cancer patients, Burkard studies cancers in which cells contain too many chromosomes, a condition called polyploidy.

About 14 percent of breast cancers and 35 percent of pancreatic cancers have three or more sets of chromosomes, instead of the usual two sets. Many other cancers have cells containing defective chromosomes rather than too many or too few.

“Our goal in the laboratory has been to find ways to develop new treatment strategies for breast cancers with too many chromosome sets,” he says.  The original goal of the current study was to make human cells that have extra chromosomes sets. But after following the accepted recipe, they unexpectedly observed the new form of cell division.

Until now, Burkard and most cell biologists today accepted a century-old hypothesis developed by German biologist Theodor Boveri, who studied sea urchin eggs. Boveri surmised that faulty cell division led to cells with abnormal chromosome sets, and then to the unchecked cell growth that defines cancer. With accumulated evidence over the years, most scientists have come to accept the hypothesis.

Normal cell division is at the heart of an organism’s ability to grow from a single fertilized egg into a fully developed individual. More than a million-million rounds of division must take place for this to occur. In each division, one mother cell becomes two daughter cells.

Even in a fully grown adult, many kinds of cells are routinely remade through cell division.

The fundamental process of cells copying themselves begins with a synthesis phase, when a duplicate copy is made of cell components, including the DNA-containing chromosomes in the nucleus. Then during mitosis, the two sets are physically separated in opposite directions, while still being contained in one cell. Finally, during cytokinesis, the one cell is cut into two daughter cells, right at the end of mitosis.

Burkard and his team were making cells with too many chromosomes–to mimic cancer. The scientists blocked cytokinesis with a chemical and waited to see what happened.

“We expected to recover a number of cells with abnormal sets of chromosomes,” Burkard explains.

The researchers found that, rather than appearing abnormal, daughter cells ended up looking normal most of the time. Contrary to Boveri’s hypothesis, abnormal cell division rarely had long-term negative effects in human cells.

So the group decided to see how the human cells recovered normal sets of chromosomes by watching with a microscope that had the ability to take video images.

“We started with two nuclei in one cell,” Burkard says. “To our great surprise, we saw the cell pop apart into two cells without going through mitosis.”

Each of the two new cells inherited an intact nucleus enveloping a complete set of chromosomes. The splitting occurred, unpredictably, during a delayed growth phase rather than at the end of mitosis.

The scientists did a number of additional experiments to carefully make sure that the division they observed was different than cytokinesis.

“We had a hard time convincing ourselves because this type of division does not appear in any textbook,” Burkard says.

Over time, they found that only 90 percent of daughter cells had recovered a normal complement of chromosomes. Burkard would like to leverage that statistic up to 99 percent.

“If we could push the cell toward this new type of division, we might be able to keep cells normal and lower the incidence of cancer,” he says.

Burkard now thinks that among all those rounds of cell division an organism goes through, every once in a while cytokinesis can fail. And that this new division is a back-up mechanism that allows cells to recover from the breakdown and grow normally.

The group has dubbed the new type of division klerokinesis to distinguish it from cytokinesis. Burkard enlisted the help of Dr. William Brockliss, UW assistant professor of classics, to come up with the name; klero is a Greek prefix meaning “allotted inheritance.”

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Collaborators on the project include Dr. Beth Weaver, UW assistant professor of cell and regenerative biology; Dr. Alka Choudhary; Robert Lera; Dr. Melissa Martowicz and Dr. Jennifer Laffin.

To see a movie, go to: http://med.wisc.edu/files/smph/docs/for_media/movie_rpe_klerokinesis.mov.