Honeysuckle Targets Viruses.. Researchers call it a ‘Virological penicillin’ MIR2911 ( + the Original Ebola discussion )

* We are Posting our videos at request, from our clinicalnews.org site..

Honeysuckle, clinical tests may of just confirmed it is a powerful virus killer. MIR2911
– In a new study, Chen-Yu Zhang’s group at Nanjing University present an extremely novel finding that a plant microRNA, MIR2911, which is enriched in honeysuckle, directly targets influenza A viruses (IAV) including H1N1, H5N1 and H7N9. Drinking of honeysuckle soup can prevent IAV infection and reduce H5N1-induced mice death.
– Furthermore, one of their ongoing studies shows that MIR2911 also directly targets Ebola virus, which is pandemic in West Africa and is becoming a crisis of public health. Thus, MIR2911 is able to serve as the “virological penicillin” to directly target various viruses.
* Cell Research advance online publication 7 October 2014; doi: 10.1038/cr.2014.130 Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses Continue reading “Honeysuckle Targets Viruses.. Researchers call it a ‘Virological penicillin’ MIR2911 ( + the Original Ebola discussion )”

Dad’s obesity could be inherited by multiple generations

Contact: Dr. Tod Fullston tod.fullston@adelaide.edu.au 61-883-138-188 University of Adelaide

The sperm of obese fathers could increase the risk of both their children and their grandchildren inheriting obesity, according to new research from  University of Adelaide.

In laboratory studies, researchers from the University’s Robinson Institute have found that molecular signals in the sperm of obese fathers can lead to obesity and diabetes-like symptoms in two generations of offspring, even though the offspring are eating healthily.

The results of the research are published online in The FASEB Journal.

“A father’s diet changes the molecular makeup of the sperm.  With obese fathers, the changes in their sperm – in their microRNA molecules – might program the embryo for obesity or metabolic disease later in life,” says the lead author of the paper, Dr Tod Fullston, who is an NHMRC Peter Doherty Fellow with the University’s Robinson Institute, based in Dr Michelle Lane’s Gamete and Embryo Biology Group.

“For female offspring, there is an increased risk of becoming overweight or obese.  What we’ve also found is that there is an increased chance of both male and female offspring developing metabolic disease similar to type 2 diabetes.

“This is the first report of both male and female offspring inheriting a metabolic disease due to their father’s obesity,” he says.

The study also extended into the second generation of progeny, which showed signs of similar metabolic disorders, including obesity, although it was not as severe as the first generation.

Dr Fullston says even if the obese father does not show any signs of diabetes, metabolic disease similar to diabetes was being seen in two generations of their descendants.

“It’s been known for some time that the health of a mother before, during and after pregnancy can impact on her child’s health, but the father’s health during this period is often overlooked,” Dr Fullston says.

“If our laboratory studies are translatable to humans, this could be a new and as yet unexplored intervention window into the epidemic of childhood obesity.

“A focus on the mother’s health is extremely important, but we’re seeing that the father’s health is also important for conception. It’s possible that by showing additional attention to diet and exercise in the father, this could have a positive impact on his future children and grandchildren.”

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Media Contact:

Dr Tod Fullston NHMRC Peter Doherty Fellow Robinson Institute The University of Adelaide Phone: +61 8 8313 8188 tod.fullston@adelaide.edu.au

‘Junk DNA’ drives embryonic development

Contact: Heather Buschman, Ph.D. hbuschman@sanfordburnham.org 858-795-5343 Sanford-Burnham Medical Research Institute

Sanford-Burnham researchers discover that microRNAs play an important role in germ layer formation—the process that determines which cells become which organs during embryonic development

             IMAGE:   These are differentiating mouse embryonic stem cells (green = mesoderm progenitor cells, red = endoderm progenitor cells). The microRNAs identified in this study block endoderm formation, while enhancing mesoderm formation.Click here for more information.

LA JOLLA, Calif., December 3, 2012 – An embryo is an amazing thing. From just one initial cell, an entire living, breathing body emerges, full of working cells and organs. It comes as no surprise that embryonic development is a very carefully orchestrated process—everything has to fall into the right place at the right time. Developmental and cell biologists study this very thing, unraveling the molecular cues that determine how we become human.

“One of the first, and arguably most important, steps in development is the allocation of cells into three germ layers—ectoderm, mesoderm, and endoderm—that give rise to all tissues and organs in the body,” explains Mark Mercola, Ph.D., professor and director of Sanford-Burnham’s Muscle Development and Regeneration Program in the Sanford Children’s Health Research Center.

In a study published in the journal Genes & Development, Mercola and his team, including postdoctoral researcher Alexandre Colas, Ph.D., and Wesley McKeithan, discovered that microRNAs play an important role in this cell- and germ layer-directing process during development.

MicroRNA: one man’s junk is another’s treasure

MicroRNAs are small pieces of genetic material similar to the messenger RNA that carries protein-encoding recipes from a cell’s genome out to the protein-building machinery in the cytoplasm.  Only microRNAs don’t encode proteins. So, for many years, scientists dismissed the regions of the genome that encode these small, non-protein coding RNAs as “junk.”

We now know that microRNAs are far from junk. They may not encode their own proteins, but they do bind messenger RNA, preventing their encoded proteins from being constructed. In this way, microRNAs play important roles in determining which proteins are produced (or not produced) at a given time.

MicroRNAs are increasingly recognized as an important part of both normal cellular function and the development of human disease.

So, why not embryonic development, too?

Directing cellular traffic

To pinpoint which—if any—microRNAs influence germ layer formation in early embryonic development, Mercola and his team individually studied most (about 900) of the microRNAs from the human genome. They tested each microRNA’s ability to direct formation of mesoderm and endoderm from embryonic stem cells. In doing so, they discovered that two microRNA families—called let-7 and miR-18—block endoderm formation, while enhancing mesoderm and ectoderm formation.

The researchers confirmed their finding by artificially blocking let-7 function and checking to see what happened. That move dramatically altered embryonic cell fate, diverting would-be mesoderm and ectoderm into endoderm and underscoring the microRNA’s crucial role in development.

             IMAGE:   Mark Mercola, Ph.D., is a professor and program director at Sanford-Burnham Medical Research Institute.Click here for more information.

But they still wanted to know more…how do let-7 and miR-18 work? Mercola’s team went on to determine that these microRNAs direct mesoderm and ectoderm formation by dampening the TGFβ signaling pathway. TGFβ is a molecule that influences many cellular behaviors, including proliferation and differentiation. When these microRNAs tinker with TGFβ activity, they send cells on a certain course—some go on to become bone, others brain.

“We’ve now shown that microRNAs are powerful regulators of embryonic cell fate,” Mercola says. “But our study also demonstrates that screening techniques, combined with systems biology, provide a paradigm for whole-genome screening and its use in identifying molecular signals that control complex biological processes.”

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This research was funded by the California Institute for Regenerative Medicine, the U.S. National Institutes of Health (National Heart, Lung, and Blood Institute grants R33 HL088266 and R01 HL113601), and the American Heart Association.

Original paper:

Colas AR, McKeithan WL, Cunningham TJ, Bushway PJ, Garmire LX, Duester G, Subramaniam S, & Mercola M (2012). Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. Genes & development PMID: 23152446

About Sanford-Burnham Medical Research Institute

Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org.

Prenatal Damage from Dioxin Shown to Involve microRNAs

ScienceDaily (Sep. 17, 2012) — Research carried out at the University of South Carolina has identified novel mechanisms through which dioxin, a well-known environmental contaminant, can alter physiological functions, according to a study published online in the journal PLOS ONE.

The research team, which included Narendra Singh, Mitzi Nagarkatti and Prakash Nagarkatti of the USC School of Medicine, demonstrated that exposure to dioxin (TCDD) during pregnancy in an experimental mouse model can cause significant toxicity to the fetus, and specifically to the organs that produce the immune cells that fight infections. They found that dioxin alters small molecules called microRNAs, which can affect the expression of a large number of genes.

The study examined over 608 microRNAs, and 78 of these were significantly altered following exposure to dioxin. On the basis of the pattern of changes in these molecules, the team was also able to predict that dioxin can alter several genes that regulate cancer. Many other physiological systems were also affected, including those involved in reproductive, gastrointestinal, hematological, inflammation, renal and urological diseases as well as genetic, endocrine and developmental disorders.

Dioxin is a highly toxic chemical produced as a byproduct of industrial processes, such as the manufacture of herbicides or pesticides or the bleaching of paper. Because it degrades slowly in the environment and is soluble in fats, dioxin can bio-accumulate in the food chain and is often found in high concentrations in the milk and fat of animals in contaminated regions.

“Our results lend more credence to the hypothesis that fetal exposure to environmental contaminants can have life-long effects,” said Mitzi Nagarkatti. “Prenatal damage to the expression of microRNAs in the immune system could well impact the adult immune response.”

The research was supported in part by the National Institutes of Health (R01ES09098, P01AT003961, R01AT006888, R01ES019313, R01MH094755) and the Veterans Administration (VA Merit Award 1I01BX001357)

http://www.sciencedaily.com/releases/2012/09/120917124345.htm

Binding sites for LIN28 protein found in thousands of human genes

Contact: Debra Kain ddkain@ucsd.edu 619-543-6163 University of California – San Diego

Protein expression also causes changes in gene splicing

IMAGE:This is Gene Yeo, Ph.D.

Click here for more information.

A study led by researchers at the UC San Diego Stem Cell Research program and funded by the California Institute for Regenerative Medicine (CIRM) looks at an important RNA binding protein called LIN28, which is implicated in pluripotency and reprogramming as well as in cancer and other diseases.  According to the researchers, their study – published in the September 6 online issue of Molecular Cell – will change how scientists view this protein and its impact on human disease.

Studying embryonic stem cells and somatic cells stably expressing LIN28, the researchers defined discrete binding sites of LIN28 in 25 percent of human transcripts.  In addition, splicing-sensitive microarrays demonstrated that LIN28 expression causes widespread downstream alternative splicing changes –variations in gene products that can result in cancer or other diseases.

“Surprisingly, we discovered that LIN28 not only binds to the non-coding microRNAs, but can also bind directly to thousands of messenger RNAs,” said first author Melissa Wilbert, a doctoral student in the UC San Diego Biomedical Sciences graduate program.

Messenger RNA or mRNA, are RNA molecules that encode a chemical “blueprint” for the synthesis of a protein.  MicroRNAs (miRNAs) are short snippets of RNA that are crucial regulators of cell growth, differentiation, and death.  While they don’t encode for proteins, miRNAs are important for regulating protein production in the cell by repressing or “turning off” genes.

“The LIN28 protein is linked to growth and development and is important very early in human development,” said principal investigator Gene Yeo, PhD, MBA, of the Department of Cellular and Molecular Medicine, the Stem Cell Research Program and the Institute for Genomic Medicine at UC San Diego. “It is usually turned off in adult tissue, but can be reactivated, for instance, in certain cancers or metabolic disorders, such as obesity.”

Using genome-wide biochemical methods to look at the set of all RNA molecules across the transcriptome, the researchers found that LIN28 recognizes and binds to a known hairpin-like structure found on the let-7 family of miRNA, but surprisingly, this same structure is also found on mRNAs, allowing LIN28 to directly regulate thousands of targets.

“One of these targets actually encodes for the LIN28 protein itself. In other words, LIN28 helps to make more of itself,” said Yeo.  This process, known as autoregulation, helps to maintain a so-called “steady-state” system in which a protein positively regulates its own production by binding to a regulatory element of the mRNA for the gene coding it.

“Since these mRNA targets include those known to be involved in gene splicing, we also implicate LIN28 in the regulation of alternative splicing,” said Wilbert, adding that abnormal variations in splicing are often implicated in cancer and other disorders.

In the splicing process, fragments that do not typically code for protein, called introns, are removed from gene transcripts, and the remaining sequences, called exons, are reconnected.  The splicing factor proteins themselves, as well as the location where these proteins bind, dictate which pieces of the RNA are included or excluded in the final gene transcript – in much the same way that removing and inserting scenes, or splicing, can alter the plot of a movie.

The discovery of thousands of precise binding sites for LIN28 within human genes offers a novel look at the role this protein plays in development and disease processes.  For example, scientists had looked at targeting a particular miRNA called let-7 to halt cancer growth.  “But we now see that LIN28 can, in essence, bypass let-7 and find many, many other binding sites – perhaps with the same adverse effect of uncontrolled cell overgrowth,” said Yeo.  “This suggests that LIN28 itself should be the therapeutic target for diseases, rather than let-7 or other miRNAs.”

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Additional contributors to the study include, Stephanie C. Huelga, Katannya Kapeli, Thomas J. Stark, Tiffany Y. Liang, Stella X. Chen, Bernice Y. Yan, Jason L. Nathanson, Kasey R. Hutt, Michael T. Lovci, and Anthony Q. Vu, UC San Diego; Hilal Kazan and Quaid Morris, University of Toronto; Katlin B. Massirer, UC San Diego and State University of Campinas, Brazil; and Shawn Hoon, A*Star and National University of Singapore.

This study was supported in part by the National Institutes of Health (HG004659, GM084317 and NS075449), the National Institute of General Medical Sciences (T32 GM008666), and the California Institute for Regenerative Medicine (RB1-01413).

Scientists discover one of the ways the influenza virus disarms host cells

Contact: Megan Fellman fellman@northwestern.edu 847-491-3115 Northwestern University

Advantage flu virus

When you are hit with the flu, you know it immediately — fever, chills, sore throat, aching muscles, fatigue. This is your body mounting an immune response to the invading virus. But less is known about what is happening on the molecular level.

Now Northwestern University scientists have discovered one of the ways the influenza virus disarms our natural defense system. The virus decreases the production of key immune system-regulating proteins in human cells that help fight the invader. The virus does this by turning on the microRNAs — little snippets of RNA — that regulate these proteins.

The researchers, led by molecular biologist Curt M. Horvath, are among the first to show the influenza virus can change the expression of microRNA to control immune responses in human lung cells.

The findings reveal a new aspect of the interaction between the influenza virus and its host. Knowing how viruses disable the immune system to wreak havoc in the body will help researchers design therapeutics to preserve the immune response and keep people healthy. The knowledge also may be valuable for future diagnostics.

The study is published by the Journal of Biological Chemistry. The paper will appear in its final form in September.

“It’s a battle of supremacy between virus and host,” said Horvath, the senior author of the paper. “Our goal is to understand how the flu replicates in the host. Now we’ve discovered a new pathway in which the flu controls the immune response, by shutting down vital protein production. With better understanding of this mechanism, one day we may be able to customize therapeutics to target individual flu strains.”

Horvath is the Soretta and Henry Shapiro Research Professor in Molecular Biology and professor of molecular biosciences in the Weinberg College of Arts and Sciences. He also is professor of microbiology-immunology and medicine at the Feinberg School of Medicine.

A microRNA has only 17 to 24 nucleotides, and its function is to dampen or shut down the production of proteins in the body. (Proteins are the workhorses of the cell.) There are hundreds of different types of microRNAs in animals.

It’s been known for many years that when a virus such as influenza infects respiratory cells there is an immediate antiviral response at the cellular level — the first barrier for protecting the body from the virus. Most of the changes that occur are a result of antiviral gene expression.

About 10 years ago, scientists first learned about small RNA pathways called microRNAs, which regulate gene expression. This led Horvath to want to investigate the role of microRNAs in influenza virus infection and determine what they are contributing to the antiviral response. Exactly which genes might the microRNAs be targeting?

In their current study, Horvath and his team used human lung cells, infected them with the influenza A virus and looked to see which microRNAs were activated in response to the virus. They focused on six microRNAs that were found to increase in abundance during flu infection.

The researchers found the virus activated two microRNAs that turned on the genes IRAK1 and MAPK3. This resulted in a decrease in the amount of proteins that help turn on the immune response.

Essentially, the virus uses the cell mechanisms to its advantage, disarming parts of the natural antiviral system. The flu takes over the expression of microRNAs for its own purposes. The flu increases the expression of microRNA, which decreases the amount of protein and diminishes the immune response.

Having identified a specific set of microRNAs whose expression in host respiratory cells is changed by the influenza virus, Horvath next is interested at looking at the clinical outcomes. He is working with Pedro C. Avila, M.D., professor of medicine-allergy-immunology at the Feinberg School to see if the microRNAs are disregulated in patients with influenza.

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The title of the paper is “Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression.” In addition to Horvath, other authors of the paper are first author William A. Buggele and Karen E. Johnson.