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Archive - Jan 2014

January 31st

Tau-Induced Neurodegeneration Associated with Global Relaxation of Tightly-Wound DNA in Alzheimer’s Disease

In a study published online on January 26, 2014 in Nature Neuroscience, Bess Frost, Ph.D., from the Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, and co-authors, identify abnormal expression of genes, resulting from DNA relaxation, that can be detected in the brain and blood of Alzheimer's patients. The protein tau (image) is involved in a number of neurodegenerative disorders, including Alzheimer's disease. Previous studies have implicated DNA damage as a cause of neuron, or cell, death in Alzheimer's patients. Given that DNA damage can change the structure of DNA within cells, the researchers examined changes in DNA structure in tau-induced neurodegeneration. They used transgenic flies and mice expressing human tau to show that DNA is more relaxed in tauopathy. They then identified that the relaxation of tightly wound DNA and resulting abnormal gene expression are central events that cause neurons to die in Alzheimer's disease. The authors write, "Our work suggests that drugs that modify DNA structure may be beneficial for treating Alzheimer's Disease." The authors recommend, "A greater understanding of the pathway of DNA relaxation in tauopathies will allow us to identify the optimal target and explore the therapeutic potential of epigenetic-based drugs." The title of their article is, “Tau Promotes Neurodegeneration through Global Chromatin Relaxation.” [Press release] [Nature Neuroscience abstract]

Single Gene in Honeybees Influences Pollen-Basket Formation on Workers’ Hind Legs

A research team led by scientists from Wayne State University in Detroit, in collaboration with scientists from Michigan State University (MSU), has identified a single gene in honeybees that separates the queens from the workers. The scientists unraveled the gene's inner workings and published the results in the January 2014 issue of Biology Letters. The gene, which is responsible for leg and wing development, plays a crucial role in the evolution of bees' ability to carry pollen. "The gene — Ultrabithorax, or Ubx — is responsible for making hind legs different from fore legs so they can carry pollen" said Dr. Aleksandar Popadic, associate professor of biological sciences in Wayne State University's College of Liberal Arts and Science and principal investigator of the study. "In some groups, like crickets, Ubx is responsible for creating a 'jumping' hind leg. In others, such as bees, it makes a pollen basket — a 'naked,' bristle-free leg region that creates a space for packing pollen." "Other studies have shed some light on this gene's role in this realm, but our team examined in great detail how the modifications take place," added Dr. Zachary Huang, an MSU entomologist. Ubx represses the development of bristles on bees' hind legs, creating a smooth surface that can be used for packing pollen. This important discovery can be used as a foray into more commercial studies focused on providing means to enhance a bee's pollination ability – the bigger the pollen basket, the more pollen that can be packed in it and transported back to the hive. While workers have these distinct features, queens do not. The team confirmed this by isolating and silencing Ubx. This made the pollen baskets completely disappear, altered the growth of the pollen comb, and reduced the size of the pollen press.

Centrosome-Related Signaling Problem Can Cause Autosomal Recessive Primary Microcephaly

Professor Erich Nigg and his research group at the Biozentrum of the University of Basel in Switzerland have discovered an amino acid signal essential for error-free cell division. This signal regulates the number of centrosomes in the cell, and its absence results in the development of pathologically altered cells. Remarkably, such altered cells are found in people with a neurodevelopmental disorder called autosomal recessive primary microcephaly. The results of these investigations have been published online on January 30, 2014 in Current Biology. Cell division is the basis of all life. Of central importance is the error-free segregation of genetic material, the chromosomes. A flawless division process is a prerequisite for the development of healthy, new cells, whilst errors in cell division can cause illnesses such as cancer. The centrosome, a tiny cell organelle, plays a decisive role in this process. Professor Nigg’s research group at the Biozentrum of the University of Basel has investigated an important step in cell division: the duplication of the centrosome and its role in the correct segregation of the chromosomes into two daughter cells. The protein STIL has an essential function in this process. It ensures that centrosome duplicate before one half of the genetic material is transported into each of the two daughter cells. During cell division, the protein STIL is degraded. If this does not occur, the protein accumulates in the cell, which then causes an overproduction of centrosomes. As a consequence, mis-segregated chromosomes are incorporated into the daughter cells, which then represent cells with faulty genetic material.

Gastric Bypass and Mysterious Recovery from Type 2 Diabetes

The majority of gastric bypass patients mysteriously recover from their type 2 diabetes within days, before any weight loss has taken place. A study at Lund University Diabetes Centre in Sweden has now shown that the insulin-producing beta cells increase in number and performance after the surgery. "We have suspected this for a while, but there have not previously been any models to prove it," says Dr Nils Wierup, who led the research. The small study involved gastric bypass surgery on just four pigs, but is the only study of its kind and therefore unique. The results confirm that neither weight loss nor reduced food intake are required in order for the procedure to raise the number of beta cells, as the pigs had identical body weight and ate exactly the same amount of food. Type 2 diabetes develops when the body's insulin-producing beta cells stop working, or when the body is not able to use the insulin that the cells produce. The majority of people who suffer from obesity and undergo a gastric bypass operation recover from their diabetes within days of the procedure. The operation involves altering the connection between the stomach and the intestines so that food bypasses the stomach and parts of the small intestine and instead goes straight into the small intestine. Until now, it has been a mystery why patients' blood sugar levels normalize. The group at Lund University Diabetes Centre found that the pigs' beta cells improve their insulin secretion. The researchers also studied tissue from the pigs' pancreas, the organ where the beta cells are located, something that is almost impossible to do in humans. They found that the number of beta cells increased after the operation. The group have previously studied the effects of gastric bypass on humans.

Wolves Are Better Imitators of Conspecifics Than Dogs, Learning More Effectively

Although wolves and dogs are closely related, they show some striking differences. Scientists from the Messerli Research Institute at the University of Veterinary Medicine, Vienna have undertaken experiments that suggest that wolves observe one another more closely than dogs and so are better at learning from one another. The scientists believe that cooperation among wolves is the basis of the understanding between dogs and humans. Their findings have been published online on January 29, 2014 in an open-access article in PLOS ONE. Wolves were domesticated more than 15,000 years ago and it is widely assumed that the ability of domestic dogs to form close relationships with humans stems from changes during the domestication process. But the effects of domestication on the interactions between the animals have not received much attention. The point has been addressed by Dr. Friederike Range and Dr. Zsófia Virányi, two members of the University of Veterinary Medicine, Vienna (Vetmeduni Vienna) who work at the Wolf Science Center (WSC) in Ernstbrunn, Niederösterreich. The scientists found that wolves are considerably better than dogs at opening a container, providing they have previously watched another animal do so. Their study involved 14 wolves and 15 mongrel dogs, all about six months old, hand-reared and kept in packs. Each animal was allowed to observe one of two situations in which a trained dog opened a wooden box, either with its mouth or with its paw, to gain access to a food reward. Surprisingly, all of the wolves managed to open the box after watching a dog solve the puzzle, while only four of the dogs managed to do so. Wolves more frequently opened the box using the method they had observed, whereas the dogs appeared to choose randomly whether to use their mouth or their paw.

January 30th

Scientists Determine the ARF-Related Effects of Auxins on DNA in Plants

A joint study published in Cell by the teams headed by Dr. Miquel Coll at the Institute for Research in Biomedicine (IRB Barcelona) and the Institute of Molecular Biology of the CSIC (Consejo Superior de Investigationes Cientificas), both in Barcelona, and Dr. Dolf Weijers at the University of Wageningen, in the Netherlands, has unravelled the mystery behind how the plant hormones called auxins activate multiple vital plant functions through various gene transcription factors. Auxins are plant hormones that control growth and development, that is to say, they determine the size and structure of the plant. Among their many activities, auxins favor cell growth, root initiation, flowering, fruit setting, and delay ripening. Auxins have practical applications and are used in agriculture to produce seedless fruit, to prevent fruit drop, and to promote rooting, in addition to being used as herbicides. The biomedical applications of these hormones as anti-tumor agents and to facilitate somatic cell reprogramming (the cells that form tissues) to stem cells are also being investigated. The effects of auxins in plants were first observed by Darwin in 1881, and since then this hormone has been the focus of many studies. However, although it was known how and where auxin is synthesized in the plant, how it is transported, and the receptors on which it acts, it was unclear how a hormone could trigger such diverse processes. At the molecular level, the hormone serves to unblock a transcription factor, a DNA-binding protein, which in turn activates or represses a specific group of genes. Some plants have more than 20 distinct auxin-regulated transcription factors.

Cal Tech Researchers Use Optogenetics to Show Activation of Inhibitory Neurons in Brain's Lateral Septum Increases Anxiety

According to the National Institute of Mental Health, over 18 percent of American adults suffer from anxiety disorders, characterized as excessive worry or tension that often leads to other physical symptoms. Previous studies of anxiety in the brain have focused on the amygdala, an area known to play a role in fear. But a team of researchers led by biologists at the California Institute of Technology (Caltech) had a hunch that understanding a different brain area, the lateral septum (LS), could provide more clues into how the brain processes anxiety. Their instincts paid off—using mouse models, the team has found a neural circuit that connects the LS with other brain structures in a manner that directly influences anxiety. "Our study has identified a new neural circuit that plays a causal role in promoting anxiety states," says David Anderson, the Seymour Benzer Professor of Biology at Caltech, and corresponding author of the study. "Part of the reason we lack more effective and specific drugs for anxiety is that we don't know enough about how the brain processes anxiety. This study opens up a new line of investigation into the brain circuitry that controls anxiety." The team's findings are described in the January 30, 2014 issue version of Cell. Led by Dr. Todd Anthony, a senior research fellow at Caltech, the researchers decided to investigate the so-called septohippocampal axis because previous studies had implicated this circuit in anxiety, and had also shown that neurons in a structure located within this axis—the LS—lit up, or were activated, when anxious behavior was induced by stress in mouse models. But does the fact that the LS is active in response to stressors mean that this structure promotes anxiety, or does it mean that this structure acts to limit anxiety responses following stress?

Some Lung Diseases Reversed in Mice by Manipulating Natural Pathway and Thrombospondin-1 Protein

It may be possible one day to treat several lung diseases by introducing proteins that direct lung stem cells to grow the specific cell types needed to repair the lung injuries involved in the conditions, according to new research by scientists at Boston Children's Hospital and collaborating institutions. Reporting in the January 30, 2014 issue ofCell, the researchers, led by Carla Kim, Ph.D., and Joo-Hyeon Lee, Ph.D., of the Stem Cell Research Program at Boston Children's, describe a new pathway in the lung, activated by injury, that directs stem cells to transform into specific types of cells. By enhancing this natural pathway in a mouse model, they successfully increased production of alveolar epithelial cells, which line the small sacs (alveoli) where gas exchange takes place. These cells are irreversibly damaged in diseases like pulmonary fibrosis and emphysema. By inhibiting the same pathway, the researchers ramped up production of airway epithelial cells, which become damaged in diseases affecting the lung's airways, such as asthma and bronchiolitis obliterans. Using a novel 3D culture model that mimics the environment of the lung, the researchers showed that even a single lung stem cell could be coaxed into producing alveolar and bronchiolar epithelial cells. By adding a protein known as thrombospondin-1 (TSP-1) to these cultures, they prodded the stem cells to generate alveolar cells. Dr. Kim and Dr. Lee conducted experiments using a live mouse model of fibrosis. By simply taking the endothelial cells that line the lung's many small blood vessels—which naturally produce TSP-1—and directly injecting the liquid surrounding the cultured cells into the mice, they were able to reverse the lung damage.

January 29th

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.