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Archive - Jan 29, 2014

RETRACTION URGED--Possibly Simpler and Faster Method of Creating Pluripotent Stem Cells Is Discovered

TEAM RESEARCHER ASKS FOR PAPER TO BE WITHDRAWN DUE TO LACK OF REPRODUCIBILITY. Breakthrough findings by Dr. Haruko Obokata (image) and colleagues at the RIKEN Center for Developmental Biology (CDB) in Japan look to upset the canonical views on the fundamental definitions of cellular differentiation and pluripotency. In a pair of reports published online on January 29, 2014 in Nature, Dr. Obokata shows that ordinary somatic cells from newborn mice can be stripped of their differentiation memory, reverting to a state of pluripotency in many ways resembling that seen in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The conversion process, which Obokata has named STAP (stimulus-triggered acquisition of pluripotency), requires only that the cells be shocked with a dose of sublethal stress, such as low pH or mechanical force, in order to trigger a remarkable transformation, in which the cells shrink, lose the functional characteristics specific to their somatic cell type, and enter a state of stem cell-like pluripotency. Such STAP cells show all the hallmarks of pluripotency, and contribute to chimeric mice and germline transmission when injected into early stage embryos. Even more interestingly, STAP cells show a level of plasticity that exceeds that even of ESCs and iPSCs, in that they can give rise to cells of both embryonic and extraembryonic lineages; other pluripotent stem cells typically only generate embryonic lineage cells. STAP cells also differ from stem cells in their lower ability to proliferate in culture, but Dr.

Puzzle of Bacteria’s CRISPR RNA-Guided Cas9-Based Destruction of Foreign DNA Solved

A central question has been answered regarding a protein that plays an essential role in the bacterial immune system and is fast becoming a valuable tool for genetic engineering. A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley has determined how the bacterial enzyme known as Cas9, guided by RNA, is able to identify and degrade foreign DNA during viral infections, as well as induce site-specific genetic changes in animal and plant cells. Through a combination of single-molecule imaging and bulk biochemical experiments, the research team has shown that the genome-editing ability of Cas9 is made possible by the presence of short DNA sequences known as “PAM,” for protospacer adjacent motif. “Our results reveal two major functions of the PAM that explain why it is so critical to the ability of Cas9 to target and cleave DNA sequences matching the guide RNA,” says Dr. Jennifer Doudna, the biochemist who led this study. “The presence of the PAM adjacent to target sites in foreign DNA and its absence from those targets in the host genome enables Cas9 to precisely discriminate between non-self DNA that must be degraded and self DNA that may be almost identical. The presence of the PAM is also required to activate the Cas9 enzyme.” With genetically engineered microorganisms, such as bacteria and fungi, playing an increasing role in the green chemistry production of valuable chemical products including therapeutic drugs, advanced biofuels, and biodegradable plastics from renewables, Cas9 is emerging as an important genome-editing tool for practitioners of synthetic biology.

MMP-9 Protein Presence or Absence Explains Differing Motor Neuron Susceptibility in ALS, Points to Potential Therapeutic Target

Columbia University Medical Center (CUMC) researchers have identified a gene, called matrix metalloproteinase-9 (MMP-9), that appears to play a major role in motor neuron degeneration in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The findings, made in mice, explain why most, but not all, motor neurons are affected by the disease and identify a potential therapeutic target for this still-incurable neurodegenerative disease. The study was published online on January 22, 2014 in Neuron. “One of the most striking aspects of ALS is that some motor neurons—specifically, those that control eye movement and eliminative and sexual functions—remain relatively unimpaired in the disease,” said study leader Christopher E. Henderson, Ph.D., the Gurewitsch and Vidda Foundation Professor of Rehabilitation and Regenerative Medicine, professor of pathology & cell biology and neuroscience (in neurology), and co-director of Columbia’s Motor Neuron Center. “We thought that if we could find out why these neurons have a natural resistance to ALS, we might be able to exploit this property and develop new therapeutic options.” To understand why only some motor neurons are vulnerable to ALS, the researchers used DNA microarray profiling to compare the activity of tens of thousands of genes in neurons that resist ALS (oculomotor neurons/eye movement and Onuf’s nuclei/continence) with neurons affected by ALS (lumbar 5 spinal neurons/leg movement). The neurons were taken from normal mice. “We found a number of candidate ‘susceptibility’ genes—genes that were expressed only in vulnerable motor neurons. One of those genes, MMP-9, was strongly expressed into adulthood. That was significant, as ALS is an adult-onset disease,” said co-lead author Dr. Krista J. Spiller, a former graduate student in Dr.

Engineered Molecule May Protect Brain from Detrimental Effects Linked to Diabetes

Researchers at the Hebrew University of Jerusalem have created a molecule that could potentially lower diabetic patients' higher risk of developing dementia or Alzheimer's disease. Recent studies indicate that high levels of sugar in the blood in diabetics and non-diabetics are a risk factor for the development of dementia, impaired cognition, and a decline of brain function. Diabetics have also been found to have twice the risk of developing Alzheimer's disease compared to non-diabetics. Now, researchers from the Hebrew University of Jerusalem have found a potential neuro-inflammatory pathway that could be responsible for the increases of diabetics' risk of Alzheimer's and dementia. They also reveal a potential treatment to reverse this process. The research group led by Professor Daphne Atlas, of the Department of Biological Chemistry in the Alexander Silberman Institute of Life Sciences at the Hebrew University, experimented with diabetic rats to examine the mechanism of action that may be responsible for changes in the brain due to high sugar levels. The researchers found that diabetic rats displayed high activity of enzymes called MAPK kinases, which are involved in facilitating cellular responses to a variety of stimuli, leading to inflammatory activity in brain cells and the early death of cells. The study shows that the diabetic rats given a daily injection of the sugar-lowering drug rosiglitazone for a month enjoyed a significant decrease in MAPK enzyme activity accompanied by a decrease in the inflammatory processes in the brain. According to the authors, this finding represents the first unequivocal evidence of a functional link between high blood sugar and the activation of this specific inflammatory pathway in the brain.

Nanophotonic System of “Chameleon of the Sea” May Inspire Improved Paints, Cosmetics, Electronics, and Military Camouflage

Scientists at Harvard University in Boston and the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, hope new understanding of the natural nanoscale photonic device that enables a small marine animal to dynamically change its colors will inspire improved protective camouflage for soldiers on the battlefield. The cuttlefish, known as the "chameleon of the sea," can rapidly alter both the color and pattern of its skin, helping it blend in with its surroundings and avoid predators. In a paper published online on January 29, 2014 in the Journal of the Royal Society Interface, the Harvard-MBL team reports new details on the sophisticated biomolecular nanophotonic system underlying the cuttlefish’s color-changing ways. "Nature solved the riddle of adaptive camouflage a long time ago," said Dr. Kevin Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at the Harvard School of Engineering and Applied Sciences (SEAS) and core faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard. “Now the challenge is to reverse-engineer this system in a cost-efficient, synthetic system that is amenable to mass manufacturing." In addition to textiles for military camouflage, the findings could also have applications in materials for paints, cosmetics, and consumer electronics. The cuttlefish (Sepia officinalis) is a cephalopod, like squid and octopuses. Neurally controlled, pigmented organs called chromatophores allow it to change its appearance in response to visual clues, but scientists have had an incomplete understanding of the biological, chemical, and optical functions that make this adaptive coloration possible.