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Archive - Jan 2016

Date

January 31st

Codiak BioSciences Closes $61 Million Series B Financing; New Funds Increase Support for a World Leader in Exosome Biology to $92 Million

On January 26, 2016, Codiak BioSciences, Inc., a leading company in the field of exosome biology, announced the closing of its $61 million Series B round, bringing total investment in its combined Series A and B financing, announced in November 2015, to $92 million. Codiak intends to use the proceeds of this round primarily to advance research and clinical development of exosomes for therapeutic and diagnostic purposes. The Series A and B financing were co-led by ARCH Venture Partners and Flagship Ventures, with participation by the Alaska Permanent Fund, Alexandria Venture Investments, and the Fidelity Management and Research Company. "This financing is a strong indication of the promise of exosomes to improve human health," said Douglas E. Williams, Ph.D., President and CEO of Codiak BioSciences. "With these additional resources we will continue to build our world-class team to realize the broad transformative potential of exosomes for multiple therapeutic and diagnostic uses." Exosomes are tiny membrane-bounded sacs, or vesicles, that are released by both healthy and cancerous cells. Substances from cell cytoplasm, including genomic DNA, various RNA species, proteins, and lipids can be encapsulated into exosomes and are shed into the extracellular environment. All fluids in the human body have been shown to contain exosomes, which can transfer the cytoplasmic ingredients to other cells either locally or at distant sites. The cytoplasmic payload within exosomes, once transferred to the recipient cells, can alter the biology of the recipient cells. Exosomes may be useful for diagnostic purposes because they contain genomic DNA for mutational analysis using a simple blood test.

Leafcutter Ant Activity Extensively Documented in Multiple Videos by University of Oregon Research Team

Deploying multiple video cameras in a University of Oregon lab, scientists have documented never-before-seen views of leafcutter ants at work processing leaves and growing their food supply in their nests. In a open-access article published online on January 27, 2016 in Royal Society Open Science, Robert Schofield, Ph.D., and colleagues detail the ants' prehensile skills and shed new insights on the various behaviors associated with gathering leaves, delivering the leaves to their nests, and processing the leaves to grow the fungus that nourishes the leafcutter ant colony. The article is titled “Leaf Processing Behaviour in Atta Leafcutter Ants: 90% of Leaf Cutting Takes Place Inside the Nest, and Ants Select Pieces That Require Less Cutting.” Leafcutter ants are agricultural pests that range from the southern United States through much of South America. Their complex societies rely on a division of labor inside and outside their often-massive underground nests. Studying the ants, Dr. Schofield said, helps find ways to reduce the damages they and their nest cause and to gather nature-based insights that may prove helpful to efforts to manufacture tiny machines and tools. In the study, Dr. Schofield's six-member team documented how leafcutters hold, lick, scrape, cut, and puncture the leaves they use. The study found that the ants are selective, choosing leaf pieces that are small and easy for them to transport, and that 90 percent of the processing work takes place in their nests. The study links to a six-minute summary video that puts the findings together and also to shorter videos that focus on individual aspects of the ants' work. The videos emerged from more than 70 hours of observations in a leafcutter colony established in Dr. Schofield's lab.

Different Schizophrenia Symptoms Linked to Different Brain Anatomy Anomalies in Corpus Collosum by Using Diffusion Tensor MRI Technique

An international team, made up of researchers from the University of Granada in southern Spain, the Washington University School of Medicine in St. Louis, and the University of South Florida, in Tampa, has linked various symptoms of schizophrenia with anatomical characteristics of the brain, by employing magnetic resonance imaging (MRI). Their research, published in the October 15, 2015 issue of the academic journal NeuroImage, could herald a significant step forward in the diagnosis and treatment of schizophrenia. The article is titled “Decomposition of Brain Diffusion Imaging Data Uncovers Latent Schizophrenias with Distinct Patterns of White Matter Anisotropy.” In what may be a major breakthrough, the scientists have successfully linked the symptoms of the illness with the brain's anatomical features, using sophisticated brain-imaging techniques. By analyzing the brain's anatomy, the scientists have demonstrated the existence of distinctive subgroups among patients diagnosed with schizophrenia, who suffer from different symptoms. In order to carry out the study, the researchers employed a magnetic resonance imaging (MRI) technique called "diffusion tensor imaging" on 36 healthy subjects and 47 schizophrenic subjects. The tests conducted on the schizophrenic subjects revealed that they had various abnormalities in certain parts of their corpus callosum, a bundle of neural fibers that connects the right and left cerebral hemispheres and is considered essential for effective interhemispheric communication. When the researchers detected anomalies in the brain's entire corpus callosum, they discovered that certain characteristic features revealed in the brain scans coincided with specific schizophrenic symptoms. For instance, patients with specific features in a particular part of the corpus callosum exhibited strange and disorganized behavior.

Human Predation Likely Contributed to Extinction of Giant Australian Bird ~47,000 Years Ago

The first direct evidence that humans played a substantial role in the extinction of the huge, wondrous beasts inhabiting Australia some 50,000 years ago, in this case a 500-pound bird, has been discovered by a team led by University of Colorado at Boulder (CU-Boulder) scientists. The flightless bird, known as Genyornis newtoni, was nearly 7 feet tall and appears to have lived in much of Australia prior to the establishment of humans on the continent ~50,000 years ago, said CU-Boulder Professor Gifford Miller, Ph.D. The evidence consists of diagnostic burn patterns on Genyornis eggshell fragments that indicate humans were collecting and cooking its eggs, thereby reducing the birds' reproductive success. "We consider this the first and only secure evidence that humans were directly preying on now-extinct Australian megafauna," said Dr. Miller, Associate Director of CU-Boulder's Institute of Arctic and Alpine Research. "We have documented these characteristically burned Genyornis eggshells at more than 200 sites across the continent." An open-access article describing this new work was published online on January 29, 2016 in Nature Communications. The article is titled “Human Predation Contributed to the Extinction of the Australian Megafaunal Bird Genyornis newtoni ~47 ka.” In analyzing unburned Genyornis eggshells from more than 2,000 localities across Australia, primarily from sand dunes where the ancient birds nested, several dating methods helped researchers determine that none of the eggshells were less than ~45,000 years old. Burned eggshell fragments from more than 200 of those sites, some only partially blackened, suggest pieces were exposed to a wide range of temperatures, said Dr. Miller, also a professor in CU-Boulder's Department of Geological Sciences.

Heterozygote Advantage in Disease Resistance May Explain Enigmatic Coexistence of Rh+ and Rh- Blood Groups in Humans

A new study published online on January 26, 2016 in PLoS ONE shows that the incidence and morbidity of many diseases and disorders correlate negatively with frequencies of Rh+ heterozygotes (i.e., the carriers of one copy of the gene for Rh positivity and one copy of the gene for Rh negativity) in the population of individual countries. At the same time, the disease burden associated with the same disorders correlated positively with frequency of Rh- subjects in individual countries. Together with the observed worse health status and higher incidence of many disorders in Rh- subjects published by the same research team last autumn, this result probably solves the 80-years-old enigma of coexistence of carriers of two variants of Rhesus gene in the same population. Rhesus factor polymorphism has been an evolutionary puzzle since its discovery in 1939. Carriers of the rarer allele should be eliminated by selection against Rhesus positive children born to Rhesus negative mothers. The new open-access PLOS ONE article is titled “Heterozygote Advantage Probably Maintains Rhesus Factor Blood Group Polymorphism: Ecological Regression Study.” Professor Jaroslav Flegr, Division of Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic is the author of the PLOS ONE paper and he said the following: “One enigma has been probably solved, however, two new [ones] have arisen. The first one is: how is it possible that the correlation of the disease burden and the frequency of particular genotypes have not been described much earlier when all necessary data are available at World Health Organization pages and the analyses can be performed within a few hours. Similarly, data showing worse health status of Rh-negative subjects are available in many databases, including the large Scandinavian nationwide databases.

January 29th

How Specialized Enzymes Remodel Chromatin to Make Genes More or Less Accessible to Gene Expression Machinery

An international team of biologists has discovered how specialized enzymes remodel the extremely condensed genetic material (chromatin) in the nucleus of cells in order to control which genes can be used. The scientists described this discovery on January 27, 2016 in an article published online in Nature. The article is titled “Genome-Wide Nucleosome Specificity and Function of Chromatin Remodellers in ES Cells.” It was known that the DNA in cells is wrapped around proteins in structures called nucleosomes that resemble beads on a string. These structures allow the genetic material to be folded and compacted into a structure called chromatin. "We knew that the compaction into chromatin makes genes inaccessible to the cellular machinery necessary for gene expression, and we also knew that enzymes opened up the chromatin to specify which genes were accessible and could be expressed in a cell, but until now, we didn't know the mechanism by which these enzymes functioned," said B. Franklin Pugh, Ph.D., Evan Pugh Professor, Willaman Chair in Molecular Biology, and Professor of Biochemistry and Molecular Biology at Penn State University and one of the two corresponding authors for the paper, along with Matthieu Gérard. Ph.D., of the University of Paris-Sud in France. The discovery was achieved by an international collaboration of scientists from the Alternative Energies and Atomic Energy Commission in France (Commissariat à l'énergie atomique et aux énergies alternatives), the National Center for Scientific Research in France (Centre national de la recherche scientifique), the University of Paris-Sud in France, Southern Medical University in Guangzhou in China, and Penn State University in the United States.

January 29th

Supplying Copper to the CNS in the Form of CuATSM Halts Progression of ALS/Lou Gehrig’s Disease in Established Mouse Model

On January 28, 2016, researchers at Oregon State University (OSU) announced that they, and colleagues, had essentially stopped the progression of amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, for nearly two years in one type of mouse model used to study the disease - allowing the mice to approach their normal lifespan. The findings, scientists indicate, are some of the most compelling ever produced in the search for a therapy for ALS, a debilitating and fatal disease, and were published online on January 27, 2015 in an open-access article in Neurobiology of Disease. The article is titled “Copper Delivery to the CNS by CuATSM Effectively Treats Motor Neuron Disease in SODG93A Mice Co-Expressing the Copper-Chaperone-for-SOD.” The new approach to ALS treatment arose from an hypothesis that sought to explain a curious observation that had previously been made in the mouse model for ALS that is based on over-expression of mutant copper/zinc superoxide dismutase (SOD). Such over-expression induces ALS-like disease in mice and this has become the most widely used model of neurodegeneration. However, no pharmaceutical agent in 20 years has extended lifespan of these ALS-model mice by more than a few weeks. The copper-chaperone-for-SOD (CCS) protein completes the maturation of SOD by inserting copper, but paradoxically human CCS causes mice co-expressing mutant SOD to die within two weeks of birth. The OSU researchers sought to explain this paradox by the hypothesis described below. The OSU researchers hyypothesized that co-expression of CCS creates a copper deficiency in the spinal cord, and therefore, the OSU team treated ALS-model mouse pups with the PET-imaging agent CuATSM, which is known to deliver copper into the CNS within minutes.

Brief Activity of Proneural Proteins Critical to Normal Neurogenesis Is Regulated by Reversible Phosphorylation of Highly Conserved Region in These Proteins

Dr. Bassem Hassan’s team at the VIB Center for the Biology of Disease in Leuven, Belgium, together with international colleagues, has discovered a previously unknown mechanism that is highly conserved between and among species, and that regulates neurogenesis through precise temporal control of the activity of a small family of proteins essential for brain development: namely, the proneural proteins. This newly described mechanism, a simple reversible phosphorylation of a highly conserved region in proneural proteins, is critical for the production of a sufficient number of neurons, their differentiation, and the development of the nervous system. The discovery of this critically important mechanism was reported in the January 28, 2016 issue of the prestigious journal Cell. The Cell article is titled “Post-Translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis.” One of the senior authors of the article is Dr. Huda Zoghbi of the Baylor College of Medicine. Our nervous system is made up of an astonishing diversity of neurons. And yet, only a very small number of proteins are needed to generate and determine the identity of these billions of neurons. An even smaller number of proteins, called proneural proteins, initiate and regulate brain development and neurogenesis (i.e., the manufacture of functional neurons from neural stem cells). These proneural proteins are transcription factors, meaning that they control the expression of other proteins by regulating the transcription of DNA to mRNA. Proneural proteins are expressed very transiently during early neurogenesis. A key aspect of this system, which remains to be elucidated, is the precise temporal regulation of the activity of the proneural proteins and the manner in which this regulation contributes to neural differentiation.

January 27th

New Fluorescent Dye Quickly & Simultaneously Detects Phosphate & Biothiol in Living Cells; Test May Enable Early Diagnosis of Diseases Such As Osteoporosis, Alzheimer’s, Type 2 Diabetes, and Prostate Cancer

Scientists from the University of Granada (UGR) in southern Spain have developed a new fluorescent dye capable of detecting, in a single test lasting just 20 minutes, the presence of phosphate and biothiol inside living cells. This scientific breakthrough could contribute significantly to the early diagnosis of diseases such as osteoporosis, Alzheimer’s, type 2 diabetes, and prostate cancer, because abnormal levels of both substances are associated with these diseases. In a paper published online on October 2, 2015 in Chemistry-A European Journal, the researchers, who work at the UGR’s Department of Physical Chemistry, illustrate the design, synthesis, and photophysical studies carried out with this new fluorescent dye. The article is titled “New Dual Fluorescent Probe for Simultaneous Biothiol and Phosphate Bioimaging.” The senior and corresponding author of the study, Luis Crovetto González, Ph.D., explains: “We have successfully managed to create, for the first time, a dual-function dye capable of detecting both substances in the same test. Until now, this procedure has been conducted using two separate fluorescent dyes and/or two separate tests.” In 2014, the same research group patented a new non-invasive method that allows for the measurement, in real-time, of concentration levels of phosphate ions inside living cells. This new dye that they have developed is, in effect, the continuation of this previous research and subsequent patent. The importance of being able to measure phosphate ions stems precisely from the fact that these measurements can be employed to assess the bioavailability of drugs used to treat certain diseases, including osteoporosis.

Antarctic Fungi Survive Mars-Like Conditions on International Space Station in Outer Space

European scientists have gathered tiny fungi that normally take shelter in Antarctic rocks and have sent them to the International Space Station (ISS). After 18 months on board the ISS in conditions similar to those on Mars, more than 60% of the fungal cells remained intact, with stable DNA. The results provide new information for the search for life on Mars. Lichens from the Sierra de Gredos (Spain) and the Alps (Austria) also traveled into space for the same experiment. The McMurdo Dry Valleys, located in the Antarctic Victoria Land, are considered to be the most similar earthly equivalent to land on Mars. These Antarctic valleys make up one of the driest and most hostile environments on our planet, where strong winds scour away even snow and ice. Only so-called cryptoendolithic microorganisms, capable of surviving in cracks in rocks, and certain lichens can withstand such harsh climatological conditions. A few years ago a team of European researchers traveled to these remote valleys to collect samples of two species of cryptoendolithic fungi: namely, Cryomyces antarcticus and Cryomyces minteri. The aim was to send these fungi to the ISS so that they could be subjected to Martian conditions, and to space, to observe their responses. The tiny fungi were placed in cells (1.4 centimeters in diameter) on an experiment platform known as EXPOSE-E, developed by the European Space Agency to withstand extreme environments. The platform was sent in the Space Shuttle Atlantis to the ISS and placed outside the Columbus module (see photo) with the help of an astronaut from the team led by Belgian Frank de Winne. For 18 months, half of the Antarctic fungi were exposed to Mars-like conditions.