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Archive for the ‘Interesting Studies’ Category

Stressed Out Cells Shut Off Protein Production

 :: Posted by American Biotechnologist on 09-12-2014

Living cells are like miniature factories, responsible for the production of more than 25,000 different proteins with very specific 3-D shapes. And just as an overwhelmed assembly line can begin making mistakes, a stressed cell can end up producing misshapen proteins that are unfolded or misfolded.

Now Duke University researchers in North Carolina and Singapore have shown that the cell recognizes the buildup of these misfolded proteins and responds by reshuffling its workload, much like a stressed out employee might temporarily move papers from an overflowing inbox into a junk drawer.

The study, which appears Sept. 11, 2014 in Cell, could lend insight into diseases that result from misfolded proteins piling up, such as Alzheimer’s disease, ALS, Huntington’s disease, Parkinson’s disease, and type 2 diabetes.

“We have identified an entirely new mechanism for how the cell responds to stress,” said Christopher V. Nicchitta, Ph.D., a professor of cell biology at Duke University School of Medicine. “Essentially, the cell remodels the organization of its protein production machinery in order to compartmentalize the tasks at hand.”

The general architecture and workflow of these cellular factories has been understood for decades. First, DNA’s master blueprint, which is locked tightly in the nucleus of each cell, is transcribed into messenger RNA or mRNA. Then this working copy travels to the ribosomes standing on the surface of a larger accordion-shaped structure called the endoplasmic reticulum (ER). The ribosomes on the ER are tiny assembly lines that translate the mRNAs into proteins.

When a cell gets stressed, either by overheating or starvation, its proteins no longer fold properly. These unfolded proteins can set off an alarm — called the unfolded protein response or UPR – to slow down the assembly line and clean up the improperly folded products. Nicchitta wondered if the stress response might also employ other tactics to deal with the problem.

In this study, Nicchitta and his colleagues treated tissue culture cells with a stress-inducing agent called thapsigargin. They then separated the cells into two groups — those containing mRNAs associated with ribosomes on the endoplasmic reticulum, and those containing mRNAs associated with free-floating ribosomes in the neighboring fluid-filled space known as the cytosol.

The researchers found that when the cells were stressed, they quickly moved mRNAs from the endoplasmic reticulum to the cytosol. Once the stress was resolved, the mRNAs went back to their spots on the production floor of the endoplasmic reticulum.

“You can slow down protein production, but sometimes slowing down the workflow is not enough,” Nicchitta said. “You can activate genes to help chew up the misfolded proteins, but sometimes they are accumulating too quickly. Here we have discovered a mechanism that does one better — it effectively puts everything on hold. Once things get back to normal, the mRNAs are released from the holding pattern.”

Interestingly, the researchers found that shuttling ribosomes between the ER and the cytoplasm during stress only affected the subset of mRNAs that would give rise to secreted proteins like hormones or membrane proteins like growth factor receptors — the types of proteins that set off the stress response if they’re misfolded. They aren’t sure yet what this means.

Nicchitta is currently searching for the factors that ultimately determine which mechanisms cells employ during the stress response. He has already pinpointed one promising candidate, and is looking to see how cells respond to stress when that factor is manipulated.

Thanks to Duke University for contributing this story.

Why are Women Underperforming Men in the Biology Classroom?

 :: Posted by American Biotechnologist on 09-02-2014

Science, technology, engineering and mathematics (STEM) fields are traditionally heavily dominated by males, which is of great concern to universities as they try to improve student retention and achievement. One exception to that trend is in the field of biology. Of undergraduate biology majors, more than 60 percent are female and about half of biosciences graduate students are women.

Given that, a common assumption is that biology is one STEM field that no longer faces gender inequalities. However, researchers with Arizona State University and University of Washington have proven otherwise. In the largest analysis of gender differences known of in introductory college-level biology courses, researchers have found evidence of gender-based gaps in both achievement and class participation.

The findings appear in the current issue of Cell Biology Education — Life Sciences Education. The American Society for Cell Biology publishes the quarterly journal.

“Often, gender differences are assumed to be present only in fields where males outnumber females and where there is a strong emphasis on math,” said Sara Brownell, assistant professor with ASU’s School of Life Sciences. “But we are seeing it in undergraduate biology classrooms that do not focus on math — where females make up about 60 percent of the class — indicating that this could potentially be a much more systemic problem. It’s likely this is not unique to physics or biology, but rather true of most undergraduate classrooms.”

Researchers studied 23 classes at a research one (R1) university over a two-year period. The courses included mostly sophomores and biology majors, and were generally taught by two instructors each. Of more than 5,000 students enrolled in the courses, nearly 60 percent were female.

After studying exam performance and class participation, scientists discovered that even with similar college GPAs, female students had average exam scores of 2.8 percent lower than male students. In addition, while female and male students were equally likely to ask a question during class, when asked to volunteer responses to questions, 63 percent of males on average spoke up — even though they comprised only 40 percent of the classroom.

Co-author Sarah Eddy, a postdoctoral scholar at the University of Washington, says the gender gap in the classroom, along with performance equality, present problems.

“Introductory biology classes are the first opportunities for many students to interact with professionals and peers in their intended fields,” said Eddy. “This is a critical opportunity to build up their confidence so that they can succeed in the field. Part of building that confidence is gaining recognition from their classmates and instructors. If females aren’t heard as often as males, they don’t have the same opportunity to succeed as biology majors.”

Brownell and her team suggest that in order to improve student retention and achievement in biology, new strategies must be put into place.

What can instructors do to level the playing field? To positively affect the participation differences in large classes, the researchers recommend using a pre-sorted list of student names to randomly call on them, rather than allowing students to raise their hands. Brownell and her team say that while students may be resistant to the method at first, it is a more equitable way to structure classroom discussions.

“In order to solve the problem, instructors must be aware that it even exists,” shared Brownell. “That’s really the point of this paper — to illustrate that there are gender differences that should not exist. The next steps are to try to determine what causes these differences and then develop additional strategies that instructors can use to lessen those differences.”

Thanks to Arizona State University for contributing this story.

Cancer Leaves a Common Fingerprint on DNA

 :: Posted by American Biotechnologist on 08-26-2014

Regardless of their stage or type, cancers appear to share a telltale signature of widespread changes to the so-called epigenome, according to a team of researchers. In a study published online in Genome Medicine on Aug. 26, the investigators say they have found widespread and distinctive changes in a broad variety of cancers to chemical marks known as methyl groups attached to DNA, which help govern whether genes are turned “on” or “off,” and ultimately how the cell behaves. Such reversible chemical marks on DNA are known as epigenetic, and together they make up the epigenome.

“Regardless of the type of solid tumor, the pattern of methylation is much different on the genomes of cancerous cells than in healthy cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine, molecular biology and genetics, oncology, and biostatistics at the Johns Hopkins University School of Medicine. Feinberg led the new study along with Rafael Irizarry, Ph.D., a professor of biostatics at Harvard University and the Dana-Farber Cancer Institute. “These changes happen very early in tumor formation, and we think they enable tumor cells to adapt to changes in their environment and thrive by quickly turning their genes on or off,” Feinberg says.

Feinberg, along with Johns Hopkins University School of Medicine oncology professor Bert Vogelstein, M.D., first identified abnormal methylation in some cancers in 1983. Since then, Feinberg’s and other research groups have found other cancer-associated changes in epigenetic marks. But only recently, says Feinberg, did researchers gain the tools needed to find out just how widespread these changes are.

For their study, the research team took DNA samples from breast, colon, lung, thyroid and pancreas tumors, and from healthy tissue, and analyzed methylation patterns on the DNA. “All of the tumors had big blocks of DNA where the methylation was randomized in cancer, leading to loss of methylation over big chunks and gain of methylation in smaller regions,” says Winston Timp, Ph.D., an assistant professor of biomedical engineering at Johns Hopkins. “The changes arise early in cancer development, suggesting that they could conspire with genetic mutations to aid cancer development,” he says.

The overall effect, Feinberg says, appears to be that cancers can easily turn genes “on” or “off” as needed. For example, they often switch off genes that cause dangerous cells to self-destruct while switching on genes that are normally only used very early in development and that enable cancers to spread and invade healthy tissue. “They have a toolbox that their healthy neighbors lack, and that gives them a competitive advantage,” Feinberg says.

“These insights into the cancer epigenome could provide a foundation for development of early screening or preventive treatment for cancer,” Timp says, suggesting that the distinctive methylation “fingerprint” could potentially be used to tell early-stage cancers apart from other, harmless growths. Even better, he says, would be to find a way to prevent the transition to a cancerous fingerprint from happening at all.

Thanks to Johns Hopkins Medicine for contributing this story.

Single gene controls jet lag

 :: Posted by American Biotechnologist on 08-13-2014

Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep and wake rhythms.

The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night-shift workers or jet lagged travelers adjust to time differences more quickly. The results, published in eLife, can point to treatment strategies for sleep problems caused by a variety of disorders.

“It’s possible that the severity of many dementias comes from sleep disturbances,” says Satchidananda Panda, a Salk associate professor who led the research team. “If we can restore normal sleep, we can address half of the problem.”

Read more…

A Revolution in Scientific Publication

 :: Posted by American Biotechnologist on 07-30-2014

Since we are talking about impact factors and Journal related stuff, (see When JIF Becomes a Dirty Word), I wanted to share with you a very cool concept that I saw recently in F1000 Research.

Aside from it’s move to the digital world, scientific publication, as we know it, has remained relatively constant for over four hundred years. Papers are written in a scientific method-based theme and broken down into bite size sections. Papers are very much there for scientists to communicate their findings with us and for the investigators to provide us with their personal interpretation of the data. While a sort of 2-way communication often happens via editorials and personal communication, the presentation of the data remains static and one dimensional. Results, which represent the heart of the researchar, often presented in tabular or pictorial format. Much of the effort and funding allocated to a research project can be distilled down to several figures and maximizing the communicative ability of these results is essential to successful publication. That is why the methodology used to publish a recent paper in the journal F1000 Research may, in fact, revolutionize the world of scientific publishing.

In the newly released article, German professor of neurogenetics, Bjorn Brembs, published a proof-of-concept figure allowing readers and reviewers to run the underlying code within the online article. Instead of presenting readers with a static figure that can only be interpreted by the author, Dr. Brembs submitted the figure’s underlying code to the journal, allowing readers and reviewers to render the figure in various formats giving them more control over interpretation of the original data.

According to Brembs, the ultimate goal is to set up all journal submissions in such a way that authors will no longer have to deal with figures. They will simply need to submit text with links to data and code, and the rest will be up to the reader.

The recent rise in retraction rates of scientific articles proves that attempts at reproducibility by other labs are crucial to cross-checking our understanding of science. With only one or two figures to choose from in the past, authors were incentivized to pick the view of the data that best demonstrated their conclusions. “The traditional method of publishing still used by most journals today means that as a referee or reader, the data cannot be reused nor can the analysis be checked to see if all agree with the reported conclusions”, said Brembs. “This slows down scientific discovery. We are pleased to be able to pioneer these two interactive figures with F1000Research, which will hopefully be the start of a big shift in the way journals treat their figures.”