Environmental Factor, October 2011, National Institute of Environmental Health Sciences
Extramural papers of the month
By Jerry Phelps
- Carbon nanotubes: Cells bite off more than they can chew
- Widespread RNA/DNA mismatch
- Reprogramming adult fibroblasts into functional neurons
- Mold exposure during infancy increases risk of asthma
Carbon nanotubes: Cells bite off more than they can chew
NIEHS-supported researchers report on the mechanics of how cells begin to engulf carbon nanotubes, only to discover too late their cause is doomed. Carbon nanotubes closed on one end appear like spheres to the cells. The cells begin to engulf the rounded end and often orient the nanotube so that it is perpendicular to the cell membrane. As the nanotube brushes up against the membrane, special receptors send signals causing the cell to wrap its membrane around the nanotube and tip it to a 90-degree angle, effectively reducing the amount of energy needed for the cell to engulf what it senses as a small particle.
Once the engulfing process begins, there is no corresponding signal to stop and reverse the process. Within minutes, the cell senses it will not be able to completely engulf the nanotube. After that, an immune response is mounted that can result in chronic inflammation, very similar to the reaction of cells to asbestos fibers.
Carbon nanotubes have been touted to have a variety of uses in material science and also in medicine as targeted drug delivery devices. The team will continue this line of research with nanotubes with blunt ends or nanoribbons to determine if these structures are less harmful to cells.
Citation: Shi X, von dem Bussche A, Hurt RH, Kane AB, Gao H(https://www.ncbi.nlm.nih.gov/pubmed/21926979) . 2011. Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. Nat Nanotechnol; doi: 10.1038/nnano.2011.151 [Online 18 September 2011].
Widespread RNA/DNA mismatch
University of Pennsylvania grantees report that when DNA is transcribed into RNA, the RNA copy is a lot less exact than previously thought. These mistakes or differences result in proteins that do not exactly match the genes that encode them, suggesting a new unexplored area of variation in the human genome.
The researchers sequenced the genomes of 27 individuals. They found more than ten thousand places where the RNA did not match the DNA. At first, they thought the differences might be attributable to technical problems, but numerous experiments confirmed the results. While performing these extra experiments, they noticed that, many times, a single RNA base was changed in exactly the same manner. For example, a site that should be AA was always AC. Every individual would either have the original AA or the edited AC, but no other possible combination.
These changes resulted in protein differences that ranged from minor single amino acid substitutions, to a protein that was 55 amino acids longer than it should have been. At this point, the researchers do not know how these changes occur or the implications of the resulting differences in protein structure and function. Further research is necessary to understand any effects resulting from these changes, such as differences in susceptibility to certain diseases.
Citation: Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, Cheung VG(https://www.ncbi.nlm.nih.gov/pubmed/21596952) . 2011. Widespread RNA and DNA sequence differences in the human transcriptome. Science 333(6038):53-58.
Reprogramming adult fibroblasts into functional neurons
An NIEHS-supported research team reports accomplishing direct reprogramming of human fibroblasts into functional neurons. The reprogrammed cells look and act like typical neurons and represent a possible step forward in treating neurodegenerative diseases.
Previously, research teams have produced functional neurons from pluripotent stem cells; however, the harvesting of pluripotent stem cells is fraught with ethical and legal issues. Somatic cells have been converted to stem cells and then differentiated into neuronal cells, but this technique is also not without issues, in that some research indicates that the technique can induce the cells to become cancerous.
The California-based researchers report that a combination of a microRNA and two transcription factors is sufficient to directly reprogram human primary dermal fibroblasts into functional neurons under controlled conditions. The induced neurons exhibit morphology, form synapses, and exhibit action potentials just like typical neurons.
These findings could have major implications in disease modeling, neurodevelopment research, and for cell-replacement therapies for neurodegenerative diseases.
Citation: Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, Ding S(https://www.ncbi.nlm.nih.gov/pubmed/21802386) . 2011. Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9(2):113-118.
Mold exposure during infancy increases risk of asthma
Children who live in moldy homes are three times more likely to develop asthma by age 7, according to new NIEHS-funded research. The researchers point out that genetic factors also play a role in early asthma development, as children whose parents have asthma are at the greatest risk.
The children were part of the Cincinnati Childhood Allergy and Air Pollution Study, a long-term effort that includes more than 700 children, with 176 identified at birth as being at high risk to develop asthma based on family history. Mold exposure levels were measured using a new tool developed by the EPA that combines 36 different mold types into one index, which accurately described the mold burden in the children's homes.
By age seven, 36 of the 176 children had developed asthma. Children living in homes with high mold content at one year of age were more than twice as likely to develop asthma. The timing of the exposure seems to be critical because living in high mold homes later in life was not correlated with developing asthma. Of all the other factors examined, only dust mite allergy and parental asthma were linked to asthma development. Air-conditioning reduced the risk of asthma.
The results of this study suggest that parents of young children should pay careful attention to poor water drainage and other issues that contribute to mold development in their homes, especially if the parents themselves have a medical history of asthma.
Citation: Reponen T, Vesper S, Levin L, Johansson E, Ryan P, Burkle J, Grinshpun SA, Zheng S, Bernstein DI, Lockey J, Villareal M, Khurana Hershey GK, Lemasters G(https://www.ncbi.nlm.nih.gov/pubmed/21802019) . 2011. High environmental relative moldiness index during infancy as a predictor of asthma at 7 years of age. Ann Allergy Asthma Immunol 107(2):120-126. Story(https://factor.niehs.nih.gov/2011/september/science-asthma/index.cfm)
(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training.)