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Archive - Sep 2015

September 25th

Exosome-Associated miRNA Secreted by Endometrium May Stimulate Expression of Adhesion Molecules by Pre-Implantation Embryo

A team of researchers from the University of Valencia in Spain and the Stanford University School of Medicine in the United States has reported data suggesting that miRNAs from the maternal endometrium (image) may act as transcriptomic modifiers of the pre-implantation embryo. In particular, the researchers showed, by microarray profiling, that six of 27 specific, maternal miRNAs were differentially expressed in the human endometrial epithelium during the window of implantation, a brief phase of endometrial receptivity to the blastocyst, and were released into the endometrial fluid. Further investigation revealed that hsa-miR-30d (Homo sapiens miRNA-30d), the expression levels of which were most significantly upregulated, was secreted from the endometrium as an exosome-associated molecule. In rodent experiments, exosome-associated hsa-miR-30d and free hsa-miR-30d were internalized by mouse embryos via the trophectoderm, resulting in an indirect overexpression of genes encoding for certain molecules involved in the murine embryonic adhesion phenomenon, namely, Itgb3, Itga7, and Cdh5. The researchers added that this finding was supported by evidence in vitro: i.e., treating murine embryos with miR-30d resulted in a notable increase in embryo adhesion. As background, the authors noted that during embryo implantation, the blastocyst interacts with and regulates the endometrium, and endometrial fluid secreted by the endometrial epithelium nurtures the embryo. The new data was reported in the September 15, 2015 issue of Development. The article is titled “Hsa-miR-30d, Secreted by the human Endometrium, Is Taken up by the Pre-Implantation Embryo and Might Modify Its Transcriptome.”

[Development abstract]

New Report Assesses Potential Multibillion-Dollar Global Liquid Biopsy Markets Out to 2020; Cell-Free DNA, Circulating Tumor Cells, and Exosomes Included; 15 Countries Detailed

A new report, entitled “LIQUID BIOPSY MARKETS Global Market Size, Strategies, and Forecasts 2015 to 2020,” is now available from Report Buyer (https://www.reportbuyer.com/product/3250897/liquid-biopsy-markets-global...). Published in August 2015, the report is 213 pages long and was prepared by Howe Sound Research. The report suggests that "blood tests replace surgical biopsies to create a new multibillion dollar market opportunity.” The screening test opportunity is explored. The report suggests that new technology that definitively identifies disease conditions from blood samples is poised to replace expensive invasive surgical biopsy procedures. The market is still in its infancy, but has outstanding growth potential, the report producers claim. In fact, it has the biggest numbers we've seen in the Clinical Diagnostics space, the producers say. The impact on the health care industry is enormous, according to the study. The report forecasts the market size out to 2020. In addition the report looks at potential market sizes by country, by cancer, and by the three different opportunities: detection, management, and screening. This independent research will, the producers say, give you the facts to speak with authority. Circulating tumor cells? Cell-free DNA? Exosomes? Find out about the technology in readily understandable terms that explain the jargon. Find the opportunities and the pitfalls. Understand growth expectations and the ultimate potential market size. The report includes detailed breakouts for 15 countries and 4 regions along, with specific breakouts for lung, breast, colorectal, prostate, and other cancers. All report data is available in Excel format on request.

Newly Discovered CRISPR/Cpf1 Editing System May Be Superior to Revolutionary CRISPR/Cas9 System for Genome Editing; Eric Lander Calls It “New Generation of Genome-Editing Technology”

A team including one of the scientists credited with harnessing the revolutionary CRISPR/Cas9 system for mammalian genome editing has now identified a different CRISPR system with the potential for even simpler and more precise genome engineering. In a study published online on September 25, 2015 in Cell, Dr. Feng Zhang (photo) and his colleagues at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT, together with co-authors Dr. Eugene Koonin at the National Institutes of Health, Dr. Aviv Regev of the Broad Institute and the MIT Department of Biology, and Dr. John van der Oost at Wageningen University in the Netherlands, describe the unexpected biological features of this new system and demonstrate that it can be engineered to edit the genomes of human cells. The Cell article is titled “Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System.” "This has dramatic potential to advance genetic engineering," said Dr. Eric Lander, Director of the Broad Institute and one of the principal leaders of the human genome project. "The paper not only reveals the function of a previously uncharacterized CRISPR system, but also shows that Cpf1 can be harnessed for human genome editing and has remarkable and powerful features. The Cpf1 system represents a new generation of genome editing technology." Dr. Lander was not involved in the current research. CRISPR sequences were first described in 1987 and their natural biological function was initially described in 2010 and 2011. The application of the CRISPR/Cas9 system for mammalian genome editing was first reported in 2013, by Dr. Zhang and separately by Dr. George Church at Harvard. In the new study, Dr.

After 100 Years in Captivity, A Genomic Look at the World’s Last Truly Wild Horses, the Przewalski’s Horses of Mongolia and China

In the 1870s, the world's last truly wild horses, known as Przewalski's horses, lived in the Asian steppes of Mongolia and China. Przewalski's horses became extinct in the wild in the 1960s, but survived in captivity, thanks to major conservation efforts. The current population is still endangered, with just 2,109 individuals, one-quarter of which live in Chinese and Mongolian reintroduction reserves. These horses descend from a founding population of 12 wild-caught Przewalski's horses and possibly up to four domesticated individuals. Now, researchers, reporting online in the Cell Press journal Current Biology on September 24, 2015, have sequenced the complete genomes of eleven Przewalski's horses, including all of the founding lineages and five historical, museum specimens dating back more than a century, and compared them to the genomes of 28 domesticated horses to provide a detailed look at the endangered animals, both past and present. The Current Biology article is titled “"Evolutionary Genomics and Conservation of the Endangered Przewalski's Horse.” "The novelty of our approach is to have not only surveyed the present-day genomic diversity of Przewalski's horses, but also to monitor their past genomic diversity, leveraging on museum specimens," says Dr. Ludovic Orlando of the University of Copenhagen's Natural History Museum of Denmark. "That way we could assess the genetic impact of more than 100 years of captivity in what used to be a critically endangered animal." The genomic evidence helps to solve a long-standing debate in horse evolution, regarding the relationships between wild and domestic horses. The ancestors of Przewalski's horses and domesticated horses remained connected by gene flow for a long time after their divergence, some 45,000 years ago, the researchers report.

Chip-Based, Field-Usable Device Developed for Amplification-Free Detection of Ebola Virus and Other Viral Pathogens

A team led by researchers at the University of California, Santa Cruz (UC Santa Cruz) has developed chip-based technology for reliable detection of Ebola virus and other viral pathogens. The system uses direct optical detection of viral molecules and can be integrated into a simple, portable instrument for use in field situations where rapid, accurate detection of Ebola infections is needed to control outbreaks. Laboratory tests using preparations of Ebola virus and other hemorrhagic fever viruses showed that the system has the sensitivity and specificity needed to provide a viable clinical assay. The team reported its results in an open-access article published on September 25, 2015 in Nature Scientific Reports. The article is titled “Optofluidic Analysis System for Amplification-Free, Direct Detection of Ebola Infection.” An outbreak of Ebola virus in West Africa has killed more than 11,000 people since 2014, with new cases occurring recently in Guinea and Sierra Leone. The current gold standard for Ebola virus detection relies on PCR to amplify the virus's genetic material for detection. Because PCR works on DNA molecules and Ebola is an RNA virus, the reverse transcriptase enzyme is used to make DNA copies of the viral RNA prior to PCR amplification and detection. "Compared to our system, PCR detection is more complex and requires a laboratory setting," said senior author Dr. Holger Schmidt, the Kapany Professor of Optoelectronics at UC Santa Cruz. "We're detecting the nucleic acids directly, and we achieve a comparable limit of detection to PCR and excellent specificity." In laboratory tests, the system provided sensitive detection of Ebola virus, while giving no positive counts in tests with two related viruses, Sudan virus and Marburg virus.

Omeprazole May Work Synergistically with Praziquantel Against Schistosomiasis

Schistosomiasis is a neglected tropical disease caused by parasitic worms endemic in parts of Africa, Southeast Asia, and Central and South America. It is currently treated by the drug praziquantel which, while both effective and cost-efficient, does not prevent reinfection after the disease has cleared. Praziquantel is the only current treatment, and while no resistance has been observed in humans, animal models predict that repeated rounds of treatment may lead to the evolution of drug resistance. It is therefore important to explore both alternative treatments and synergistic therapies to expand the lifetime and effectiveness of the praziquantel treatment. Researchers from the University of Sao Paulo in Brazil used a gene expression microarray to explore how the gene expression of adult worms was affected by a sub-lethal dose of praziquantel. Previous research had found differences between male and female worms, and the researchers found further differences between females from mixed-sex infection either joined to males in a mating pair, or unpaired. Females from mixed-sex infections unpaired with males were more likely to down-regulate their gene expression in response to praziquantel (77% of genes down-regulated). Conversely, paired females were more likely to up-regulate their genes in response to treatment, with 98% of affected genes up-regulated. The researchers also looked for genes that could act as potential targets for new therapies. They found a promising target in a gene affected in all the worms that coded for a type of proton pump. The proton pump was homologous to a protein found in humans and targeted by the proton pump inhibitor drug omeprazole.

Tongues of Alpine Bumble Bees Shorten in Response to Climate-Related Changes in Flower Diversity

Climate-related changes in flower diversity have resulted in a decrease in the length of alpine bumble bees' tongues, a new study reports, leaving these insects poorly suited to feed from and pollinate the deep flowers they were adapted to previously. The study was published in an open-access article in the September 25, 2015 issue of Science is is titled “Functional Mismatch in a Bumble Bee Pollination Mutualism under Climate Change.” The results highlight how certain mutually beneficial ecological partnerships can be lost due to shifts in climate. Many co-evolved species have precisely matched traits; for example, long-tongued bumble bees are well adapted for obtaining nectar from deep flowers with long corolla tubes. Recent studies suggest long-tongued bumble bees are declining in number. To better understand why, Dr. Nicole Miller-Struthman, of SUNY College at Old Westbury, together with colleagues, studied several high-altitude sites in Colorado where two species of long-tongued alpine bumblebee live. Using bumble bee specimens from 1966 through 1980, and from 2012 through 2014, the researchers measured changes in tongue length, and noticed a significant shortening. Next, using archived bee specimens and field surveys of bumble bees and host plants, they examined possible mechanisms for this change. It was not a result of decreasing body size, competition from invaders, or co-evolution with flowers in the area, they report. Instead, it is a result of warming summers, which reduced numbers of the deep flowers these species preferred, forcing the insects to be general foragers capable of feeding across remaining flowers, including many shallow flowers. The pattern seen here may predict future effects of climate change in other systems, the authors say.

Enamel First Evolved in Skin and Only Colonized Teeth Much Later

When did the enamel that covers our teeth evolve? And where in the body did this tissue first appear? In an article published online on September 23, 2015 in Nature, researchers from Uppsala University in Sweden and the Institute of Vertebrate Palaeontology and Palaeoanthropology (IVPP) in Beijing, China, combine data from two very different research fields, paleontology and genomics, to arrive at a clear but unexpected answer to this question: enamel originated in the skin and colonized the teeth much later. The Nature article is titled “New Genomic and Fossil Data Illuminate the Origin of Enamel.” We are all familiar with enamel. It is shiny and white; this tissue gleams back at us from the bathroom mirror every morning when we brush our teeth. It is the hardest substance produced by the body, composed almost entirely of the mineral apatite (calcium phosphate) deposited on a substrate of three unique enamel matrix proteins. Like other land vertebrates we only have teeth in the mouth, but certain fishes such as sharks also have "dermal denticles" - little tooth-like scales - on the outer surface of the body. In many fossil bony fishes, and a few archaic living ones such as the gar (Lepisosteus) from North America, the scales are covered with an enamel-like tissue called "ganoine." Dr. Tatjana Haitina, a researcher in the Department of Organismal Biology, Uppsala University, investigated the genome of Lepisosteus, which was sequenced by the Broad Institute, and found that it contains genes for two of our three enamel matrix proteins: the first to be identified from a ray-finned bony fish. Furthermore, these genes are expressed in the skin, strongly suggesting that ganoine is a form of enamel. But where did enamel originate - in the mouth, in the skin, or both at once?

Harvard Study Suggests Spinal Muscular Atrophy (SMA), a Sometimes Fatal Genetic Disease of Childhood, and ALS (Lou Gehrig’s Disease) Both Involve Activation of a Motor Neuron Stress Response, But in Different Ways

Harvard Stem Cell Institute (HSCI) researchers studying spinal muscular atrophy (SMA) have found what they term "surprising similarities" between this childhood disorder that attacks motor neurons and the disease amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig's disease. The findings have been published online on August 27, 2015 in the journal Cell Stem Cell. The article is titled “Genome-Wide RNA-Seq of Human Motor Neurons Implicates Selective ER Stress Activation in Spinal Muscular Atrophy.” The research team, led by HSCI principal faculty member Dr. Lee Rubin, uncovered molecular changes that explain, at least in part, why motor neurons rather than other types of neurons or other types of cells are affected by the SMA illness. Unlike ALS and other neurodegenerative diseases, which tend to manifest later in life, SMA strikes infants. Unlike ALS, SMA is a genetic disorder that causes a range of outcomes, with the milder form leaving some children confined to wheelchairs, and the more severe form causing paralysis and death before the second birthday. Though not as well-known as ALS, SMA is "the most frequent fatal genetic disease of young children," said Dr. Rubin, a Professor in Harvard's Department of Stem Cell and Regenerative Biology (HSCRB). About one in 50 people are carriers of SMA and about one in 5,000 children are born with the disease. Dr. Rubin said researchers are still working to determine the mechanisms of SMA. "It has never been clear why motor neurons, which relay signals from the brain to the muscles via the spinal column, die selectively," Dr. Rubin said.

Study Finds Genetic Differences Between Relapsing and Non-Relapsing Breast Cancers; Results May Drive Further Personalized Medicine Efforts; Importance of Genetic Analysis of New Metastases When Making Treatment Decisions Is Emphasized

Although most patients with breast cancer are cured after treatment, in about one in five, the cancer will recur, returning either to the same place as the original tumor or spreading to other parts of the body (metastasis). Now, researchers have taken an important step towards understanding why some primary breast cancers return while others do not. The researchers have found that the genetic factors driving the cancers that recur are different from those found in the cancers that do not. This discovery could enable doctors to identify patients at high risk of their cancer returning and to target the genes responsible for recurrence when the cancer is first diagnosed in order to prevent its return. Presenting the results to the 2015 European Cancer Congress on Saturday, September 26, 2015, in Vienna, Austria, Lucy Yates, M.D., a clinical research oncologist from the Wellcome Trust Sanger Institute, Cambridge, UK, will say that her team analyzed data from the genetic sequencing of 1,000 breast cancer patients' tumours. In 161 cases this included samples taken from recurring tumors or metastases. They compared the cancer genes found in cancers sampled at first diagnosis (primary tumors) with those found in relapsed cancers. The European Cancer Congress 2015 is the 18th congress of the European CanCer Organization (ECCO) and the 40th congress of the European Society for Medical Oncology (ESMO). The title of Dr. Yates’ presentation is “The Driver Landscape of Breast Cancer Metastasis and Relapse." (Abstract Number 1804). The researchers found that there were genetic differences between primary and recurring tumors, with some differences being acquired during the later phases when the cancers recurred and started to spread. The scientists say these findings have important implications for personalized medicine.