Syndicate content

Archive - Mar 2017

March 29th

Social Bees Have Kept Their Gut Microbes for 80 Million Years

Approximately 80 million years ago, a group of bees began exhibiting social behavior, which includes raising young together, sharing food resources and defending their colony. Today, their descendants--honey bees, stingless bees, and bumble bees--carry stowaways from their ancient ancestors: five species of gut bacteria that have evolved along with the host bees. These bacteria, living in the guts of social bees, have been passed from generation to generation for 80 million years, according to a new study published in the March 29, 2017 issue of Science Advances and led by researchers at The University of Texas at Austin. The article is titled “Dynamic Microbiome Evolution in Social Bees.” The published finding adds to the argument that social creatures, like bees and humans, not only transfer bacteria among one another in their own lifetime--they have a distinctive relationship with bacteria over time, in some cases even evolving on parallel tracks as species. "The fact that these bacteria have been with the bees for so long says that they are a key part of the biology of social bees," says Nancy Moran, Ph.D., Professor of Integrative Biology at UT-Austin, who co-led the research with postdoctoral researcher Dr. Waldan Kwong. "And it suggests that disrupting the microbiome, through antibiotics or other kinds of stress, could cause health problems." Most insects, including nonsocial bees, do not have specialized gut microbes. Because they have limited physical contact with individuals of their own species, they tend to get their microbes from their environment. Social bees, on the other hand, spend much time in close contact with one another in the hive, making it easy to transfer gut microbes from individual to individual.

Simple Blood Test May Unlock New Frontier in Treating Depression; C-Reactive Protein Level Test Can Indicate Effective Antidepressant Medication for Individual Patient; "Can Immediately Be Used in Clinical Practice"

For the first time, doctors can determine which medication is more likely to help a patient overcome depression, according to research that pushes the medical field beyond what has essentially been a guessing game of prescribing antidepressants. A blood test that measures a certain type of protein level (level of C-reactive protein) provides an immediate tool for physicians who, until now, have relied heavily on patient questionnaires to choose a treatment, said Dr. Madhukar Trivedi, who led the research at the University of Texas (UT) Southwestern Medical Center's Center for Depression Research and Clinical Care. "Currently, our selection of depression medications is not any more superior than flipping a coin, and yet that is what we do. Now we have a biological explanation to guide treatment of depression," said Dr. Trivedi, Director of the Center for Depression Research and Clinical Care, a cornerstone of UT Southwestern's Peter O'Donnell Jr. Brain Institute. The study demonstrated that measuring a patient's C-reactive protein (CRP) levels through a simple finger-prick blood test can help doctors prescribe a medication that is more likely to work. Utilizing this test in clinical visits could lead to a significant boost in the success rate of depressed patients who commonly struggle to find effective treatments. A major national study (STAR*D) Dr. Trivedi led more than a decade ago gives insight into the prevalence of the problem: Up to a third of depressed patients don't improve during their first medication, and about 40 percent of people who start taking antidepressants stop taking them within three months. "This outcome happens because they give up," said Dr. Trivedi, whose previous national study established widely accepted treatment guidelines for depressed patients.

Japanese Researchers Illuminate Enzymatic Process That Produces Bilirubin, the Anti-Oxidant Molecule That, in Excess, Is Associated with Jaundice

Jaundice, marked by yellowing of the skin, is common in infants, but is also a symptom of various adult diseases. This discoloration is caused by excess bilirubin (BR), the substance that gives bile its yellow tinge. However, BR is also a vital antioxidant, which at healthy levels protects cells against peroxide damage. Its production in the body, though, has long been a source of uncertainty. Now, a Japanese research collaboration involving Osaka University and other Japan institutions believes it has the answer. BR is already known to be produced from a related chemical, biliverdin (BV), by the enzyme biliverdin reductase (BVR). The enzyme wraps around BV and transfers two hydrogen atoms – one positive and one negative – to produce the yellow antioxidant. However, biologists could not establish which part of the enzyme was chemically involved in the process (the active site), or where the positive hydrogen came from. The new findings, revealing this information, were published online on February 7, 2017 in Nature Communications. The open-access article is titled “A Substrate-Bound Structure of Cyanobacterial Biliverdin Reductase Identifies Stacked Substrates As Critical for Activity.” “Previous studies used BVR from rats, and could never crystallize the enzyme well enough to determine how it binds to BV,” study co-author Keiichi Fukuyama, Ph.D., says. “We realized that the same enzyme in Synechocystis bacteria had an almost identical fold-shape, but was easier to examine by X-ray crystallography.” To their surprise, the researchers found two molecules of BV – one stacked upon the other – at the active site, even though only one is converted to BR. From the X-ray data, they deduced why two were needed.

Viruses Use Special Proteins to Thwart Bacteria’s CRISPR Anti-Virus Defense System

For many bacteria, one line of defense against viral infection is a sophisticated RNA-guided “immune system” called CRISPR-Cas. At the center of this system is a surveillance complex that recognizes viral DNA and triggers its destruction. However, viruses can strike back and disable this surveillance complex using “anti-CRISPR” proteins, though no one has figured out exactly how these anti-CRISPRs work—until now. For the first time, researchers have solved the structure of viral anti-CRISPR proteins attached to a bacterial CRISPR surveillance complex, revealing precisely how viruses incapacitate the bacterial defense system. The research team, co-led by biologist Gabriel C. Lander, Ph.D., of The Scripps Research Institute (TSRI), discovered that anti-CRISPR proteins work by locking down CRISPR’s ability to identify and attack the viral genome. One anti-CRISPR protein even “mimics” DNA to throw the CRISPR-guided detection machine off its trail. “It’s amazing what these systems do to one-up each other,” said Dr. Lander. “It all comes back to this evolutionary arms race." The new research, co-led by Blake Wiedenheft, Ph.D., of Montana State University, was published in the March 23, 2017 issue of Cell. The article is titled “Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex.” If CRISPR complexes sound familiar, that’s because they are at the forefront in a new wave of genome-editing technologies. CRISPR stands for “clustered regularly interspaced short palindromic repeats.” Scientists have discovered that they can take advantage of CRISPR’s natural ability to degrade sections of viral RNA and use CRISPR systems to remove unwanted genes from nearly any organism.

March 28th

Genentech Announces FDA Approval of OCREVUS, the First and Only Medicine for Both Relapsing and Primary Progressive Forms of Multiple Sclerosis

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today (March 28, 2017) that the U.S. Food and Drug Administration (FDA) approved OCREVUS™ (ocrelizumab) as the first and only medicine for both relapsing and primary progressive forms of multiple sclerosis. The majority of people with MS have a relapsing form or primary progressive MS at diagnosis. “The FDA’s approval of OCREVUS is the beginning of a new era for the MS community and represents a significant scientific advance with this first-in-class B-cell-targeted therapy,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development at Genentech. “Until now, no FDA-approved treatment has been available to the primary progressive MS (PPMS) community, and some people with relapsing forms of MS continue to experience disease activity and disability progression despite available therapies. We believe OCREVUS, given every six months, has the potential to change the disease course for people with MS, and we are committed to helping those who can benefit gain access to our medicine.” In two identical relapsing multiple sclerosis (RMS) Phase III studies (OPERA I and OPERA II), OCREVUS demonstrated superior efficacy on the three major markers of disease activity by reducing relapses per year by nearly half, slowing the worsening of disability, and significantly reducing MRI lesions compared with Rebif® (high-dose interferon beta-1a) over the two-year controlled-treatment period. A similar proportion of people in the OCREVUS group experienced a low rate of serious adverse events and serious infections compared with people in the high-dose interferon beta-1a group in the RMS studies.

Nanopore Translocation of Knotted DNA Rings Examined in New Study

Anyone who has been on a sailing boat knows that tying a knot is the best way to secure a rope to a hook and prevent its slippage. The same applies to sewing threads where knots are introduced to prevent them slipping through two pieces of fabric. How, then, can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of various biological systems? This is the fascinating question addressed by Dr. Antonio Suma and Dr. Cristian Micheletti, researchers at the International School for Advanced Studies (Scuola Internazionale Superiore di Studi Avanzati or SISSA) in Trieste, Italy, who used computer simulations to investigate the options available to the genetic material in such situations. The study was published online on March 28, 2017 in PNAS. The article is titled “Pore Translocation of Knotted DNA Rings.” "Our computational study sheds light on the latest experimental breakthroughs on knotted DNA manipulation and adds interesting and unexpected elements," explains Dr. Micheletti. "We first observed how knotted DNA filaments pass through minuscule pores with diameter of about 10 nanometers (10 billionths of a meter). The behavior observed in our simulations was in good agreement with the experimental measurements obtained by an international research team led by Dr. Cees Dekker, which were published only a few months ago in Nature Biotechnology. These advanced and sophisticated experiments marked a turning point for understanding DNA knotting. However, current experiments cannot ‘see’ how DNA knots actually pass through the narrow pore. In fact, the phenomenon occurs over a tiny spatial scale, and is therefore inaccessible to microscopes.

Antagonistic Co-Evolution Between Bacteria and Phages Is a Key Driver of Microbial Diversity in Human Gut, Scientist Suggests in Opinion Piece

What drives bacterial strain diversity in the gut? Although there are a number of possible explanations, an opinion piece published on March 22, 2017 in Trends in Microbiology by Dr. Pauline Scanlan, a Royal Society – Science Foundation Ireland Research Fellow at the APC Microbiome Institute, University College Cork, Ireland, addresses one potentially important and overlooked aspect of this unresolved question. Dr. Scanlan’s article is titled “Bacteria–Bacteriophage Coevolution in the Human Gut: Implications for Microbial Diversity and Functionality.” The human gut is host to an incredible diversity of microbes collectively known as the gut microbiome. Our gut microbiomes interact with us, their human hosts, to perform a myriad of crucial functions ranging from digestion of food to protection against pathogens. While superficially it may seem that the microbes inhabiting the human gut are stable and broadly similar between individuals, recent advances in sequencing technology that allow for high-level resolution investigations have shown that our gut microbiomes are dynamic, capable of rapid evolution, and unique to each individual in terms of bacterial species and strain diversity. This unique inter-individual variation is of crucial importance as we know that differences in bacterial strain diversity within species can have a range of positive or negative consequences for the human host – for example, some strains of a given bacteria are harmless while another strain of the same bacterial species could kill you. A classic example of this is different strains of the gut bacterium Escherichia coli - E. coli Nissle 1917 is used as a probiotic and E. coli O157:H7 has been responsible for a number of deadly food-borne pathogen outbreaks.

Chisholm-Led MIT Study of Tiny Ocean Bacterium May Offer Clues to Evolution of Entire Biosphere; Analysis of “Metabolic Networks” in Marine Ecosystems Provides Evidence for Directional Evolution Toward Increased Resources for Total System

For scientists at MIT the smallest of all photosynthetic bacteria holds clues to the evolution of entire ecosystems, and perhaps even the whole biosphere. The key is a tiny bacterium called Prochlorococcus, which is the most abundant photosynthetic life form in the oceans. New research shows that this diminutive creature’s metabolism has evolved in a way that may have helped trigger the rise of other organisms, to form a more complex marine ecosystem. Its evolution may even have helped to drive global changes that made possible the development of Earth’s more complex organisms. The research also suggests that the co-evolution of Prochlorococcus and its interdependent co-organisms can be seen as a microcosm of the metabolic processes that take place inside the cells of much more complex organisms. The new analysis was published on March 27, 2017 in PNAS in a paper by MIT’s postdoc Rogier Braakman, Ph.D., Professor Michael Follows, and Institute Professor Sallie (Penny) Chisholm (photo), who was part of the team that discovered this tiny organism and its outsized influence. The PNAS article is titled “Metabolic Evolution and the Self-Organization of Ecosystems.” “We have all these different strains that have been isolated from all over the world’s oceans, that have different genomes and different genetic capacity, but they’re all one species by traditional measures,” Dr. Chisholm explains. “So there’s this extraordinary genetic diversity within this single species that allows it to dominate such vast swaths of the Earth’s oceans.” Because Prochlorococcus is both so abundant and so well-studied, Dr. Braakman says it was an ideal subject for trying to figure out “within all this diversity, how do the metabolic networks change?

March 27th

Study Links Shorter Telomeres & Mutation-Associated Heart Disease (CAVD); Results May Enable Better Mouse Models for Study of Mutation-Associated Human Disease

Scientists at the Gladstone Institutes in San Francisco have discovered a key mechanism that protects mice from developing a human disease of aging, and begins to explain the wide spectrum of disease severity often seen in humans. Both aspects center on the critical role of telomeres, protective caps on the ends of chromosomes that erode with age. Erosion of telomeres has long been associated with diseases of aging, but how telomere length affects human disease has remained largely a mystery. Now, scientists find that shortening telomeres in mice carrying a human genetic mutation linked to heart disease results in a deadly buildup of calcium in heart valves and vessels. This innovative model allows the researchers to test viable new drugs for this disease, and it provides a potential solution to studying other human disorders of aging in mice. Calcific aortic valve disease (CAVD) causes calcium to accumulate in heart valves and vessels until they harden like bone. It can only be treated by replacing the valve through heart surgery and is the third leading cause of heart disease, affecting 3 percent of adults over the age of 75. CAVD develops with age, and it can be caused by a mutation in one of two copies of the NOTCH1 gene. Humans typically have two copies of each gene. When one copy is lost, the remaining gene may not produce enough of its protein to sustain normal function. While reducing protein levels by half often causes disease in humans, mice with the same change are frequently protected from disease, but scientists have been unsure why. In the new study, published online on March 27, 2017 in the Journal of Clinical Investigation, the Gladstone scientists linked telomere length to risk for, or resistance to, these types of diseases.

Cellular Uptake of Exosomes Appears Size-Dependent; Smaller Exosomes Taken Up More Quickly by Target Cells

Size really does matter when it comes to the mechanisms that cells use to communicate with each other, according to pioneering new nanobiotechnology research that has important implications for the diagnosis and treatment of disease. An international team of scientists has made major strides in understanding “exosomes”– tiny biological structures (or ‘vesicles’) that are believed to be used, at least in part, by cells in the body to transfer information. The researchers believe the findings could be significant for several fields of medical science, from personalizing medical treatments to better understanding the growth and spread of cancerous tumors. Exosomes can be packed with proteins and RNA. They can be generated by one cell, taken up by another, and then trigger a specific response in the second cell. To date, scientific research has focused on the content of exosomes, but a new study led by scientists at the University of Lincoln, UK, focused instead on the size of exosomes and how this affects the way they work. Led by Dr. Enrico Ferrari, a specialist in nanobiotechnology, the research team discovered that the smaller the exosomes are, the easier it is for target cells to pick them up. This makes communication between cells much faster. The study examined exosomes taken from a patient with a high-grade glioma (rapidly growing brain tumor). The researchers had previously found that some stem cells within the patient’s brain were producing exosomes that were responsible for supporting cancer cells and making them more aggressive. The scientists’ latest work suggests that the level of aggression in a tumor could be determined by the size of the exosomes produced by the cancerous cells – for example the smaller the exosomes, the faster the cells can communicate and reproduce, and the more quickly the cancer develops.