Hepatitis C: A Promising Animal Model, and Reasons to Get Tested

Hepatitis C virus infection by source, in the U.S. From Wikipedia.
Hepatitis C virus infection by source, in the U.S. From Wikipedia.

During graduate studies in Medical Microbiology and Immunology at the University of WI-Madison, a favorite class was an infectious disease course that included an exercise in designing the perfect pathogen. This was a thought experiment, a writing exercise. No laboratory experimentation was involved.

You might initially think of a perfect pathogen as one that produces the most spores, allowing the pathogen to spread or seed itself in many locations. Copious slime and mucus production and projectile vomiting and diarrhea were frequently suggested during discussions of the perfect pathogen. And it’s true that these features really get the attention of the infected person and her/his caregiver. There are some pretty scary microbial buggers out there, for instance those that cause hemolytic anemia and/or raging fevers; these are the attention getters of the infectious disease world. Continue reading “Hepatitis C: A Promising Animal Model, and Reasons to Get Tested”

Cell Line Misidentification Rears Its Ugly Head

Cancer cell illustration

Back in 2009, we reported on the problem of cell line contamination (1). In that article we reported the statistics that an estimated 15–20% of the time, the cell lines used by researchers are misidentified or cross-contaminated with another cell line (1). This presents a huge problem for the interpretation of data and the reproducibility of experiments, a key pillar in the process of science. We have revisited this topic several times, highlighting the issues cell and tissue repositories have discovered with cell lines submitted to them (2) and discussing the new guidelines issued by ANSI (3,4) for researchers regarding when during experimental processes cell lines should be authenticated and what methods are acceptable for identifying cell lines.

Just recently two papers were voluntarily retracted by their authors because of cross contamination among cell lines used in the laboratories. The first that came to my attention represented the first retraction from Nature Methods in its nine years of publication. In this paper, cross contamination of a primary gliomasphere cell lines with HEK cells expressing GFP resulted in “unexplained autofluorescence” associated with tumorigenicity (5). The second paper, retracted from Cancer Research by the original authors, was also another cross contamination story involving HEK cells (6). In this story a gene was incorrectly described as a tumor suppressor, that when silenced led to the formation of tumors in nude mice. It turns out that the contaminating HEK cells also failed to express this same gene.

So because of cross contamination of cell lines, two groups have voluntarily retracted papers. Being open and honest about what had happened with the cell lines and reaching the decision to retract the papers could not have been an easy thing, but these decisions benefit the scientific community in many ways. Obviously they benefit the researchers doing work on the specific research questions addressed by the papers by preventing researchers from pursuing paths that lead to dead ends. But in the bigger picture these retractions reinforce the argument that cell line authentication needs to become a routine and accepted part of any experimental process that depends on cell culture if we are to have confidence in the experimental results.

References

  1. Dunham, J.H. and Guthmiller, P.  (2009) Doing good science: Authenticating cell line identity. Promega Notes 101, 15–18.
  2. Duham, J.H. and Guthmiller, P. (2012) Doing good science: Authenticating cell line identity. Promega PubHub. [Internet: Accessed September 2013]
  3. Gopal, A. (2013) Fingerprinting  your cell lines. Promega Connections blog [Internet: Accessed September 2013]
  4. Sundquist, T. (2013) Preventing the heartache of cell line contamination. Promega Connections blog [Internet: Accessed September 2013]
  5. Evanko, D. (2013) A retraction resulting from cell line contaminationMethagora blog. [Internet Accessed September 2013]
  6. Negorev, D. (2013) Retraction: Sp100 as a potent tumor suppressor: Accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Can. Res. 73, 4960.

Epigenetics and Exercise

Turning on some genes
Turning on some genes

If, like me, you sometimes need more motivation to exercise consistently—even though you know that it is good for you—you may be interested in the findings of a paper published recently in PLOS Genetics. The paper showed that consistent exercise over a 6-month period caused potentially beneficial changes in gene expression. In short, regular exercise caused expression of some “good” genes, and repression of “bad” ones, and these changes appeared to be controlled by epigenetic mechanisms.

Epigenetic changes are modifications to DNA that affect gene expression but don’t alter the underlying sequence. Perhaps the best understood example of an epigenetic change is DNA methylation—where methyl groups bind to the DNA at specific sites and alter expression, often by preventing transcription. Epigenetic changes have been shown to occur throughout all stages of development and in response to environmental factors such as diet, toxin exposure, or stress. The study of epigenetics is revealing more and more about how the information stored in our DNA is expressed in different tissues at different times and under different environmental circumstances. Continue reading “Epigenetics and Exercise”

Improving Fitness Using Your Weight

Push ups, yes. But the gym not needed for this routine.
Push ups, yes. But the gym not needed for this routine.

Body weight, that is.

It’s true. One of the more recent fitness trends is that of using body weight for resistance, in conjunction with high-intensity circuit training. Brett Klika and Chris Jordan published an article on this method in the American College of Sports Medicine’s Health & Fitness Journal, in the May/June 2013 issue.

Here is the Article:
 “High-Intensity Circuit Training: Using Body Weight: Maximal Results with Minimal Investment

When it comes to fitness I’m mostly old school. Years of one- and two-a-day swim practices in high school and college, and long runs for track and cross-country practice off-season from swimming were part of the ‘more miles/time is better’ philosophy. You had to put in the time and miles to get the conditioning and strengthening, as well as cardiovascular benefits. Continue reading “Improving Fitness Using Your Weight”

Basic Biology Matters

crop image2Every scientific paper is the story of a journey from an initial hypothesis to a final conclusion. It may take months or years and consists of many steps taken carefully one at a time. The experiments are repeated, the controls verified, the negative and positive results analyzed until the story finally makes sense. Sometimes the end of the story confirms the hypothesis, sometimes it is a surprise. A paper published last week in Cell describes a study where a team of researchers investigating one problem in basic biology (how one component of a signaling complex works), found an unexpected and potentially significant application in a different field (cancer research).

The paper, published in the June 6 issue of Cell, describes a previously unknown interaction between two cellular proteins—the transcription factor HIF1A and the cyclin-dependent kinase CDK8—in the regulation of genes associated with cellular survival under low-oxygen conditions. An accompanying press release describes how the discovery of a role for CDK8 in this process may have implications for cancer research, as CDK8 may be a potential target for drugs to combat “hypoxic” tumors. Continue reading “Basic Biology Matters”

Dietary Analysis, DNA Style

dna testing of foodDNA testing methods are being used to solve problems in an ever-increasing number of fields. From crime scene analysis to tissue typing, from mammoths to Neanderthals, and from Thutmose I to Richard III, both modern mysteries and age-old secrets are being revealed. The availability of fast, accurate, and convenient DNA amplification and sequencing methods has made DNA analysis a viable option for many types of investigation. Now it is even being applied to solve such mundane mysteries as the precise ingredients used in a sausage recipe, and to answer that most difficult of questions “what exactly is in a doner kebab?” Continue reading “Dietary Analysis, DNA Style”

Cold-War Bunkers Enlisted in the Fight Against Cold-Loving Fungus: More on the White-Nose Syndrome Story

Bunkers at Aroostook National Wildlife Refuge. photo credit: USFWS/Steve Agius
Bunkers at Aroostook National Wildlife Refuge. photo credit: USFWS/Steve Agius

A lot has happened since I first wrote about White-Nose Syndrome, the fungal disease that has devastated bat populations in North America. The disease, caused by the cold-loving fungus Geomyces destructans (now renamed Psuedogymnoascus destructans), has been identified in many more places, including most recently confirmed cases in Georgia, South Carolina, Illinois and Missouri in the United States and Prince Edward Island, Canada.

Controlling the spread of this disease is a tremendous problem, because as I indicated in a previous blog post, keeping a hardy fungus from spreading among a population of densely packed small animals in tiny, cold damp areas is not a simple task.

This problem is going to require creative solutions, and scientists at the U.S. Fish and Wildlife Service may have come up with a great idea that answers two questions: How do you control the spread of White-Nose Syndrome and what do you do with 43 unused Air Force bunkers? Continue reading “Cold-War Bunkers Enlisted in the Fight Against Cold-Loving Fungus: More on the White-Nose Syndrome Story”

Antibiotics and Honey–An Old Solution for a New Problem

Antibiotic DiskThis month saw the publication of a UK Department of Health report on the growing problem of antimicrobial resistance, which included the shocking recommendation that antimicrobial resistance be added to the UK government list of threats to national security alongside terrorism and pandemic flu. In this report, Professor Dame Sally Davies, Chief Medical Officer for the UK, focused on the increasing problem of multidrug resistant organisms–raising the profile of an important issue that many scientists and health-care professionals have warned us about before. A March 12 Nature editorial welcomed the recommendations as a sign that policy makers in the UK are taking the threat of antimicrobial resistance seriously and are prepared to take more steps to address the problem of multidrug-resistant organisms. Continue reading “Antibiotics and Honey–An Old Solution for a New Problem”

Sonnets in DNA

William ShakespeareFor sixty years now, scientists have studied the role of DNA as a vehicle for the storage and transmission of genetic information from generation to generation. We have marveled at the capacity of DNA to store all the information required to describe a human being using only a 4-letter code, and to pack that information into a space the size of the nucleus of a single cell. A letter published last week in Nature exploits this phenomenal storage capacity of DNA to archive a quite different kind of information. Forget CDs, hard drives and chips, the sum of human knowledge can now be stored in synthetic DNA strands. The Nature letter, authored by scientists from the European Bioinformatics Institute in Cambridge, UK, and Agilent Technologies in California, describes a proof-of-concept experiment where synthetic DNA was used to encode Shakespeare’s Sonnets, Martin Luther King’s “I Have a Dream” speech, a picture of the Bioinformatics Institute, and the original Crick and Watson paper on the double-helical nature of DNA. Continue reading “Sonnets in DNA”

Are These the Bones of Richard III?

In central England, an archaeological dig is happening in an unlikely spot—a parking lot in the city of Leicester. The goal: To find the final resting spot of Richard III, the last of England’s Plantagenet kings and perhaps one of its most maligned rulers. Richard III reigned over England for only two years before being killed by Henry Tudor’s army during the Battle of Bosworth Field in August 1485 at the end of the War of the Roses, which pitted Richard’s House of York against the House of Lancaster. Many historical records suggest that Richard’s body was brought to Leicester and buried between the nave and altar at Grey Friars church. You would think that a king’s tomb would be well marked and well remembered, even for an unpopular king like Richard III, but that is not the case here. Henry was said to have erected a memorial for his former rival, but that and any other monuments, along with the church itself, are long gone, destroyed during the Dissolution of the Monasteries, when Henry VIII was named Supreme Head of the Church in England and systematically razed monasteries, convents and friaries throughout England, Wales and Ireland between 1536 and 1541. Since then, the exact location of Richard III’s remains was lost to history. However, thanks to a team of University of Leicester archaeologists and geneticists that might be changing.

Continue reading “Are These the Bones of Richard III?”