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Archive - Mar 2017

March 15th

Progress in Development of World's First Nanoengineered Retinal Prosthesis

A team of engineers at the University of California (UC) San Diego and La Jolla, California-based startup Nanovision Biosciences, Inc. have developed the nanotechnology and wireless electronics for a new type of retinal prosthesis that brings research a step closer to restoring the ability of neurons in the retina to respond to light. The researchers demonstrated this response to light in a rat retina interfacing with a prototype of the device in vitro. The scientists detail their work in an article published online on August 16, 2016 in the Journal of Neural Engineering. The article is titled “Towards High-Resolution Retinal Prostheses with Direct Optical Addressing and Inductive Telemetry.” The technology could help tens of millions of people worldwide suffering from neurodegenerative diseases that affect eyesight, including macular degeneration, retinitis pigmentosa, and loss of vision due to diabetes. Despite tremendous advances in the development of retinal prostheses over the past two decades, the performance of devices currently on the market to help the blind regain functional vision is still severely limited--well under the acuity threshold of 20/200 that defines legal blindness. "We want to create a new class of devices with drastically improved capabilities to help people with impaired vision," said Gabriel A. Silva, Ph.D., one of the senior authors of the work and professor in bioengineering and ophthalmology at UC San Diego. Dr. Silva also is one of the original founders of Nanovision.

March 14th

3D Visualization of the Islets of Langerhans--New Tool Available for Diabetes Research

Umeå University researchers in Sweden have created datasets that map the three-dimensional distribution and volume of the insulin-producing cells in the pancreas. The wealth of visual and quantitative information may serve as a powerful reference resource for diabetes researchers. The Umeå University researchers have published their datasets online on March 10, 2017 in Scientific Data, which is a Nature Research journal for scientifically valuable collections of research data with high reuse potential. The publication is titled “Data from: Spatial and Quantitative Datasets of the Pancreatic Β-Cell Mass Distribution in Lean and Obese Mice.” The hormone insulin -- which is needed to regulate the blood sugar levels of the body -- is produced by the pancreas and plays a key role in the development of diabetes. Insulin-producing cells are organized in the so-called Islets of Langerhans (or pancreatic islets), which are scattered by the thousands in the pancreas. In diabetes research, it is often important to study the quantity and distribution of insulin-producing cells. At present, such studies are generally based upon analyses of chosen cross-sections of pancreatic tissue. These, in turn, form the basis for attempting to gain an overall picture of the pancreas. "However, such analyses only provide limited information and are often ridden with relatively large margins of error because the conclusions are based only on two-dimensional data," says Ulf Ahlgren, Professor in Molecular Medicine at Umeå University and in charge of the publications. Dr. Ahlgren and his research colleagues at the Umeå Centre for Molecular Medicine (UCMM) have previously developed new methods to create three-dimensional images of the insulin cell distribution in intact pancreas based on so-called optical projection tomography (OPT).

New Way to Reset Gene Expression in Cancer Cells Shows Promise for Leukemia Treatment

New findings from Rockefeller University researchers could guide the development of potent combination therapies that deliver more effective and durable treatment of leukemia. In work published online on March 1, 2017 in Nature, the scientists show that it’s possible to deactivate cellular programs involved in tumor growth by disrupting a protein that regulates genes. The article is titled “ENL Links Histone Acetylation to Oncogenic Gene Expression in Acute Myeloid Leukaemia.” At the center of this research are proteins called histones, which provide a physical support structure for the genome, and can also help regulate gene expression. Chemical modifications to histones can turn nearby genes on or off, and the cell interprets these chemical marks with the help of a variety of “reader” proteins. Once they recognize and bind to the chemically modified histones, the reader proteins recruit other factors that coordinate gene activation or inhibition. This process can become derailed in cancer, and drugs that selectively inhibit a class of readers known as BET proteins have already shown early promise in treating certain tumors. Now, a multi-institutional research team—led in part by Dr. David Allis, Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics—has uncovered similar therapeutic potential for another, recently-identified class of reader proteins. These proteins share a structural feature called a YEATS domain, which specifically recognizes histones modified with a type of chemical mark called an acetyl group. “The functional importance of this reading activity by the YEATS domain was unknown,” says Dr. Liling Wan, a postdoctoral fellow in the Allis lab and lead author on the study, but she also notes strong evidence linking these proteins to cancer.

March 12th

A Closer Look at Brain Organoid Development

How close to reality are brain organoids, and which molecular mechanisms underlie the remarkable self-organizing capacities of tissues? Researchers already have succeeded in growing so-called "cerebral organoids" in a dish - clusters of cells that self-organize into small brain-like structures. Dr. Juergen Knoblich and colleagues have now further characterized these organoids and published their results online on March 10, 2017 in The EMBO Journal. The article is titled “Self‐Organized Developmental Patterning and Differentiation in Cerebral Organoids.” The scientists demonstrate that, as in the human brain, so-called forebrain organizing centers orchestrate developmental processes in the organoid, and that organoids recapitulate the timing of neuronal differentiation events found in human brains. The development of the human brain from just a few cells to a thinking organ is one of the great mysteries of biology. In the past decade, Dr. Knoblich and his team at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences have pioneered brain organoid technology to investigate this intriguing process. Understanding normal organoid development is a prerequisite to using this powerful system to explore the possibility of modeling human developmental diseases.

RNA Interference Approach Could Save Millions of Tons of Crops Each Year from Contamination with Aflatoxin, a Major Threat to Health and Food Security, Especially in Developing Parts of the World

Researchers at the University of Arizona have found a promising way to prevent the loss of millions of tons of crops to a fungus each year, offering the potential to dramatically improve food security, especially in developing countries. The team's approach uses transgenic corn plants that produce small RNA molecules that prevent fungi from producing aflatoxin, highly toxic substances that can render an entire harvest unsafe for human consumption even in small amounts. Although extensive field testing will have to precede widespread application of the new technique in agricultural settings around the world, the results of the study, published online on March 10, 2017 in Science Advances, showed that transgenic corn plants infected with the fungus suppressed toxin levels below detectable limits. Crops all over the world are susceptive to infection by fungi of various Aspergillus species, a fungus that produces secondary metabolites known as aflatoxins. These compounds have been implicated in stunting children's growth, increasing the risk for liver cancer, and making people more susceptible to diseases such as HIV and malaria. The open-access Science Advances article is titled “Aflatoxin-free transgenic maize using host-induced gene silencing.” Unlike in the U.S., where crops intended for human consumption are tested for aflatoxin and incinerated once levels approach 20 parts per billion (equivalent to one drop of water in a 22,000-gallon pool), no testing is available in many developing parts of the world, especially in Africa, where millions of people depend on consuming what they harvest. There, toxin levels up to 100,000 parts per billion have been measured, says study leader Dr. Monica Schmidt, an Assistant Professor in the UA's School of Plant Sciences and a member of the UA's BIO5 Institute.

Repeated Convergent Evolotion: How Rove Beetles Keep Evoloving into Army Ant Parasites

Marauding across the tropical forest floor, aggressive army ant colonies harbor hidden enemies within their ranks. The impostors look and smell like army ants, march with the ants, and even groom the ants. But far from being altruistic nest-mates, these creatures are parasitic beetles, engaged in a game of deception. Through dramatic changes in body shape, behavior, and pheromone chemistry, the beetles gain their hostile hosts' acceptance, duping the ants so they can feast on the colony brood. This phenomenon did not evolve just once. Instead, these beetles arose at least a dozen separate times from non-ant-like ancestors. This discovery, published online on March 9, 2017 in Current Biology, provides evidence that evolution has the capacity to repeat itself in an astonishingly predictable way. The article is titled “"Deep-Time Convergence in Rove Beetle Symbionts of Army Ants.” "These beetles represent a new and really stunning system of convergent evolution," says study co-author and evolutionary biologist Joseph Parker, Ph.D., of Columbia University and the American Museum of Natural History. "It's an elaborate symbiosis, which has evolved in a stereotyped way, multiple times from free-living ancestors." The ant-mimicking beetles all belong to the Staphylinidae, or rove beetles, but don't mistake them for close relatives: the last common ancestor of the beetles in the study lived 105 million years ago, at about the time that humans split from mice. "What's exceptional is that this convergent system is evolutionarily ancient," says Dr. Parker. Although most other convergent systems, such as Darwin's finches, three-spined stickleback, and African lake cichlid fish, are a few million years old at most, this newly discovered example extends back into the Early Cretaceous.

March 11th

Making Sense of Death-Defying Leaps by Cliff-Born Murre Chicks

Before they have the wing span to actually permit them to fly, young guillemots (also known as murres) leap hundreds of meters off towering cliffs and flutter down towards the sea, guided by their fathers. Scientists have long wondered why these tiny chicks make this remarkable leap, hoping to avoid the rocks below them, in what seems an unlikely survival strategy for a species. It had earlier been suggested that murre offspring headed off to sea once the chicks reached about one-quarter of their adult size and were large enough to defend themselves from potential predators and too large to be fed at the colony--so that this seemingly death-defying behavior could be better understood as being, in some ways, a tradeoff between the safety offered in the colony and the fast growth rates at sea, where more food is available. But after tracking the behavior of murre fathers and their offspring for six weeks in murre colonies in some of the most remote locations on the globe, in Nunavut, Greenland, and islands off Newfoundland, scientists have discovered that mortality rates were similar between chicks at sea and in the colonies. Moreover, the team, which was made up of researchers from McGill and Memorial Universities in Canada and Aarhus and Lund Universities in Denmark and Sweden, discovered that chicks at sea grew at roughly twice the speed of those at the colony, because the murre fathers no longer needed to fly back and forth to the colony to feed them. Unusually among animals, after three weeks of care by both parents, it is the father who then spends 5 to 7 weeks rearing the offspring by himself on the high seas. Meanwhile, the mother spends her time back at the colony, copulating with paramours to choose a potential suitor should her mate not return the next year. The study documented the hard work done by the father.

Castration-Resistant Prostate Cancer Cell Growth Impeded by Endostatin

Failure of hormone deprivation therapy, which is used to slow prostate cancer in patients, leads to castration-resistant prostate cancer, a lethal form of advanced disease with limited treatment options. University of Alabama at Birmingham (UAB) researchers have discovered that endostatin, a naturally occurring protein in humans, can significantly decrease proliferation of castration-resistant prostate cells in culture, and in a paper published online on January 9, 2017 in The FASEB Journal, they describe the physiological pathways and signaling evoked by endostatin. The article is titled “Endostatin Inhibits Androgen-Independent Prostate Cancer Growth by Suppressing Nuclear Receptor-Mediated Oxidative Stress." This endostatin effect is now being tested in a preclinical xenograft animal model of castration-resistant prostate cancer. "We hope we can delay the onset of castration-resistant disease," said Selvarangan Ponnazhagen, Ph.D., a UAB professor in the UAB Department of Pathology who holds an Endowed Professorship in Experimental Cancer Therapeutics at UAB. The medical treatment that deprives prostate cancer cells of androgen hormones through anti-hormone therapy creates oxidative stress in those cancer cells. This oxidative stress is associated with reactivated signaling by the androgen receptor in the cells, causing resistance to the anti-hormone therapy. The UAB researchers, led by Dr. Ponnazhagen and first author Joo Hyoung Lee, Ph.D., hypothesized that the oxidative stress might be triggered upstream of the androgen receptor, with the glucocorticoid receptor as the stress-inducer. If so, endostatin might interact with the glucocorticoid receptor to remove the oxidative stress and reduce that pro-tumorigenic function in the cancer cells, thereby preventing or delaying the onset of castration-resistant disease.

Severe Hypoglycemia Linked to Increased Risk of Death in People with Diabetes; Within Three Years of Dangerously Low Blood Sugar Episode Requiring ER Visit, One-Third of Those in Study Died

A single instance of blood sugar falling so low as to require an emergency department visit was associated with nearly double the risk of cardiovascular disease or death, according to results of a new Johns Hopkins Bloomberg School of Public Health study of older adults with type 2 diabetes. Additionally, using data from a large, longitudinal study, the researchers found that one third of the older adults with diabetes who had experienced a severe low blood sugar episode (hypoglycemia) died within three years of the incident. In analyzing their data, the researchers controlled for such variables as how severe a person's diabetes was and how long it had been since diagnosis. The researchers say that their findings suggest that doctors might want to pay special attention to patients who have been sent to the emergency department for hypoglycemia after losing consciousness, having a seizure, or experiencing another serious health event. The findings were presented on March 10, 2017 at the American Heart Association's EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Oregon. The presentation was titled “"Association of Severe Hypoglycemia with Cardiovascular Disease and All-Cause Mortality in Older Adults with Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study." "If you have a patient with a history of severe hypoglycemia, this could portend poorly for his or her future," says Alexandra K. Lee, MSPH, a Ph.D. candidate in epidemiology at the Bloomberg School. "Our thinking has been that you resolve a hypoglycemic episode and it's over.

Robber Fly's Aerial Hunting Skill Relies on Extreme Visual Acuity

You might expect that the miniature brains and eyes of tiny robber flies would limit their ability to launch sophisticated in-flight predatory attacks on their prey. But, according to researchers reporting in Current Biology on March 9, 2017 who've captured the rice-sized predators' tactics on film, that is not so. The open-access article is titled “A Novel Interception Strategy in a Miniature Robber Fly with Extreme Visual Acuity.” The movies show that robber flies sit and wait for a tempting prey item (or a bead) to fly past. Once they do, the flies take off using an interception strategy known as constant bearing angle (CBA), keeping their prey at a constant angle to ensure that they'll eventually meet. That's impressive, but there's more. Once the robber fly reaches a distance of about 30 centimeters from its target, it "locks on," slowing down and curving its flight path to make a successful catch even more likely. Their secret to pulling it off is all in the eyes. "We knew that these flies likely had an improved vision compared to other true flies, but we never imagined that they would give dragonflies, which are ten times larger, a run for their money with regards to spatial resolution of the retina," says Dr. Paloma Gonzalez-Bellido of the University of Cambridge. "Likewise, although we expected these flies to employ CBA, we were surprised by their use of a lock-on phase to ease the capture." The researchers, including Dr. Gonzalez-Bellido and Dr. Trevor Wardill, made their discovery by presenting flies in their natural habitats with beads ranging from about 1 to 4 millimeters in diameter on a fishing line. They recorded the flies' reaction to seeing one of those beads zoom past using two high-speed video cameras. The films allowed them to reconstruct the insects' precise flight trajectories in three dimensions.