Hemorrhagic Fevers Can Be Caused by Body’s Antiviral Interferon Response


Hemorrhagic fevers caused by Lassa, dengue and other viruses affect more than one million people annually and are often fatal, yet scientists have never understood why only some virus-infected people come down with the disease and others do not.

But now, virologists and immunologists at The Scripps Research Institute(TSRI) have found a major clue to the mystery of “hemorrhagic fever” syndromes. In findings reported this week in an Early Edition of theProceedings of the National Academy of Sciences, the team showed that Interferon Type I (IFN-I) immune proteins are key drivers of a viral syndrome in mice that closely mimics these human hemorrhagic fevers.

“Blocking IFN-I signaling in certain genetic mouse strains completely prevented disease signs such as vascular leakage leading to death,” said TSRI Associate Professor of Immunology Roberto Baccala, who, with TSRI Professor Michael Oldstone, led this study.

While IFN-I proteins traditionally have been considered essential for an effective antiviral response and are still used to treat some chronic viral infections, the new study suggests that these proteins sometimes do much more harm than good—and that blocking them, or specific biological pathways they activate, might be a good therapeutic strategy against hemorrhagic fevers.

Striking Impact

The discovery arose from the team’s recent research with the New Zealand Black (NZB) mouse, an inbred laboratory strain whose overactive immune system leads, in midlife, to an autoimmune condition resembling lupus. Curious to see how a viral infection in early life would affect the mice, the team injected a group of the animals with a much-studied mouse virus called lymphocytic choriomeningitis virus (LCMV).

The parental LCMV Armstrong (Clone 53b) caused no symptoms and was quickly cleared by the NZB mice. But a variant (clone 13) that is efficient at infecting cells and causing a persistent infection—yet still causes only mild disease in most other mouse strains—had a strikingly different impact, showing serious signs of illness. Seven to eight days after infection, all the NZB mice that been injected with clone 13 had died.

Further examination revealed leaky blood vessels, fluid and immune virus-specific T cell infiltration into the lungs, decreased platelet counts and other pathological signs reminiscent of human hemorrhagic fevers.

As the scientists knew, LCMV is a member of the family of viruses that includes Lassa virus, which causes one of world’s most common hemorrhagic fevers—with a high fatality rate—in a subset of infected patients. “Lassa virus and LCMV infect the same cell type via the same cell-surface receptor,” Baccala said. Lassa virus infects hundreds of thousands of individuals annually, culminating in more than 20,000 deaths per year.

Most people infected with Lassa virus experience only mild illness, yet about 20 percent develop the hemorrhagic syndrome. Dengue virus manifests similarly, causing a hemorrhagic syndrome in only a subset of patients. The pathology seen in the LCMV clone 13-infected NZB mice suggested that they could serve as useful models of these human hemorrhagic syndromes, providing clues to how they develop and therapeutic stop-points for their treatment.

A New Target

Baccala and his colleagues soon found evidence that the hyperactivity of the NZB mouse antiviral CD8 cytotoxic T cell response is chiefly to blame for its fatal hemorrhagic disease. The researchers observed powerful CD8+ T cells in higher than normal numbers in affected NZB mouse tissues and a greater number of immune-stimulating molecules on the CD8+ cells’ surfaces. This CD8+ T cell overreaction damaged the endothelial cells that line pulmonary blood vessels, causing them to become leaky, which in turn led to the fatal buildup of fluid in the lungs.

IFN-I proteins historically have been known as the chief mobilizers of the protective antiviral response. When Baccala and his colleagues blocked IFN-I signaling, up to a day after infection, the CD8+ T cell response was virtually absent, and levels of clone 13 LCMV rose sharply in the NZB mice. Under these conditions, the mice showed no sign of disease and seemed able to tolerate the high viral load indefinitely—implying that the virus itself is virtually harmless when it doesn’t prompt an immune reaction.

“We are now working to determine whether we can target IFN-I itself to treat such conditions or whether we need to target the more specific signals, downstream of IFN-I, that cause pathology,” said Baccala.

In addition to Baccala and Oldstone, the co-authors of the study, “Type I interferon is a therapeutic target for virus-induced lethal vascular damage,” were Megan J. Welch, Rosana Gonzalez-Quintial, Kevin B. Walsh, John R. Teijaro, Anthony Nguyen, Cherie T. Ng, Brian Martin Sullivan, Alessandro Zarpellon, Zaverio M. Ruggeri, Juan Carlos de la Torre and Argyrios N. Theofilopoulos, all of TSRI.

Dr. Nancy Snyderman: Cancer breakthroughs offer new hope – Health – TODAY.com


http://m.today.com/health/dr-nancy-snyderman-cancer-breakthroughs-offer-new-hope-2D79751461?sf26903810=1

From the desk of Zedie.

Energy-generating shoes.


A 15-year-old student from Philippines has invented a device that harnesses the energy of your steps to make electricity.

Soon you’ll be able to charge your mobile phone with your shoes! Angelo Casimiro has summited his project to the 2014 Google Science Fair and he has shared his tips on how to make a portable device to charge USB gadgets over at TreeHugger. All you need is a generic USB powerbank, 6 piezoelectric transducers, 4 rectifier diodes, hookup wire (at least 12″), an old pair of shoes, and adhesive tape

http://pda.sciencealert.com.au/features/20140406-25615-2.html

From the desk of Zedie.

Powerful magnetic fields challenge black holes’ pull .


Astronomers have found that magnetic forces can be as strong as gravity near supermassive black holes.

 

zoom
A computer simulation of gas (in yellow) falling into a black hole (too small to be seen).  Twin jets are also shown with magnetic field lines.
Alexander Tchekhovskoy (LBNL)

Black holes are thought to dominate their surroundings by their extremely powerful gravitational pull. However, other forces that are usually considered to be weaker are also at work near these objects. These include forces exerted by the pressure of the infalling hot gas and magnetic forces. In a surprising twist, astronomers at the Max Planck Institute for Radio Astronomy (MPIfR) and Lawrence Berkeley National Laboratory (LBNL) have found that in fact magnetic forces can be as strong as gravity near supermassive black holes.

Some black holes that are voraciously consuming interstellar gas also expel some of it in twin narrow outflows, or jets. This study focused on those supermassive black holes at the centers of galaxies that have observed radio-emitting jets.

“We realized that the radio emission from a black hole’s jets can be used to measure the magnetic field strength near the black hole itself,” says study lead author Mohammad Zamaninasab (formerly at the MPIfR and supported by a grant from Deutsche Forschungsgemeinschaft, DFG). “Our real ‘aha’ experience came when we compared our magnetic force measurements to the force of gravity near black holes and found them to be comparable.”

On a purely theoretical level, the possibility that magnetic fields may be as strong as gravity near black holes has been studied by state-of-the-art computer simulations. “When the infalling gas carries enough magnetic field in our simulations, then the magnetic field near the black hole gets stronger until it balances gravity,” explains Alexander Tchekhovskoy of LBNL, a co-author of the study. “This fundamentally changes the behavior of the gas near the black hole.”

Surprisingly, the magnetic field strength around these exotic objects is comparable to the magnetic field produced in something more familiar: an MRI machine that you can find in your local hospital. Both supermassive black holes and MRI machines produce magnetic fields that are roughly 10,000 times stronger than Earth’s surface magnetic field, which is what guides an ordinary compass.

The measurements of the magnetic field strength near the black hole were based on mapping what fraction of the radio emission is absorbed at different locations near the base of the jet. “Such observations existed for an order of hundred sources from earlier work of several international research teams using the Very Long Baseline Array, a network of radio telescopes spread across the United States,” says co-author Tuomas Savolainen from MPIfR. “A large fraction of these measurements had just relatively recently become available thanks to a large observing program called MOJAVE, which monitors several hundred jets launched by supermassive black holes.”

The strength of the magnetic field near the black hole horizon also controls how powerful its jets are and, therefore, how luminous they appear at radio wavelengths according to current theories that treat black holes as a sort of spinning magnet. Thus, it is possible that the bright radio jets emanate from those black hole systems that have magnetic fields as strong as gravity.

These results may lead to changes in how to interpret black hole observations. “If our ideas hold up to further scrutiny, then astronomers’ expectations for how to measure black hole properties would need to be changed,” concludes Eric Clausen-Brown, also from MPIfR. “Our study also changes how powerful we expect black hole jets can be, and since these jets can impact their own galaxies and beyond, we may need to rethink how much of an environmental impact black holes can have.”

Human stem cells successfully transplanted, grown in pigs — ScienceDaily


http://www.sciencedaily.com/releases/2014/06/140604105525.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily%2Ftop_news%2Ftop_science+%28ScienceDaily%3A+Top+Science+News%29

From the desk of Zedie.

No evidence of the double nature of neutrinos — ScienceDaily


http://www.sciencedaily.com/releases/2014/06/140604133820.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily%2Ftop_news%2Ftop_science+%28ScienceDaily%3A+Top+Science+News%29

From the desk of Zedie.

Women’s Battle Against Environmental Toxins Alex Jones’ Infowars: There’s a war on for your mind!


Toxic compounds in foods and beverages, in addition to other environmental factors undermining women’s health
Report: Women's Battle Against Environmental Toxins

 

www.infowars.com/womens-battle-against-environmental-toxins/

From the desk of Zedie.

New Methods for Targeted Alpha Radiotherapy.


Targeted radiotherapies based on alpha emitters are a promising alternative to beta emitting radionuclides. Because of their much shorter range, targeted α-radiotherapy (TAT) agents have great potential for application to small, disseminated tumors and micro metastases and treatment of hematological malignancies consisting of individual, circulating neoplastic cells. A promising approach to TAT is the use of the \textit{in vivo} α-generator radionuclides 223Ra (t1/2= 11.4 d) and 225Ac (t1/2= 10.0 d). In addition to their longer half-lives, these two isotopes have the potential of dramatically increasing the therapeutic efficacy of TAT as they each emit four α particles in their decay chain. This principle has recently been exploited in the development of Xofigo\textregistered , the first TAT agent approved for clinical use by the U.S. FDA. Xofigo, formulated as 223RaCl2, is used for treatment of metastatic bone cancer in men with castration-resistant prostate cancer. TAT with 223Ra works, however, only in the case of bone cancer because radium, as a chemical analogue of calcium, efficiently targets bone. In order to bring the benefits of TAT with 223Ra or 225Ac to other tumor types, a new delivery method must be devised. Retaining the \textit{in vivo} α generator radionuclides at the target site through the decay process is one of the major challenges associated with the development of TAT. Because the recoil energy of the daughter radionuclides from the α-emission is 100 keV — a value which is four orders of magnitude greater than the energy of a covalent bond – the daughters will not remain bound to the bioconjugate at the targeting site. Various approaches have been attempted to achieve retention of the α-generator daughter radionuclides at the target site, including incorporation of the \textit{in vivo} generator into liposomes and fullerenes. Unfortunately, to date single wall liposomes and fullerenes are able to retain less than 10{\%} of the daughter radionuclides. We have recently demonstrated that a multilayered nanoparticle-antibody conjugate can deliver multiple α radiations from the \textit{in vivo }α-generator 225Ac at biologically relevant receptor sites. The nanoparticles retained over 90{\%} of the 221Fr daughter over the course of three weeks in \textit{in vitro} experiments. In \textit{in vivo} experiments, approximately 90{\%} of the 213Bi was retained in the target tissue 24 hours after injection of the antibody labeled nanoparticle. An overview of the development and application of this promising, new approach to targeted alpha therapy will be presented.

The Brutally Honest Coca-Cola Commercial You’ll Never See On Television.


Coca-Cola plans to run its very first ad defending aspartame and the safety of artificial sweeteners. This move comes as a result of a dramatic drop in diet cola sales within the past year. This is great news as it goes to show how much of an impact we can really make by raising awareness about the health effects of aspartame.

http://themindunleashed.org/wp-content/uploads/2014/06/the-brutallyyy.jpg

More people around the world are making better choices and you can read more about that and the dangers associated with the Coke here.

I came across this video and thought it would be appropriate to share in light of Coca-Cola’s recent move to bring awareness to and “join together” in fighting obesity. This comes before their more recent ad campaign to defend artificial sweeteners like aspartame. It’s the brutally honest Coca-Cola commercial you’ll never see on television. This is a voiced over version of the original Coke commercial which you can see here.

http://themindunleashed.org/2014/06/brutally-honest-coca-cola-commercial-youll-never-see-television.html

From the desk of Zedie.

It’s alive! A German artist regrows Van Gogh’s ear .


German artist Diemut Strebe made a replica of Vincent van Gogh’s ear using genetic material from one of the artist’s living relatives.

Convincing Lieuwe van Gogh, the great-great-grandson of Vincent’s beloved brother Theo van Gogh, to donate a few cells for an art project was easy. Lieuwe and Vincent share one sixteenth of the same genes, and he found the idea of creating a ‘living replica’ of his great-great-uncle’s ear simply fascinating.

VanGogh_Strebe

On December 23, 1888, Van Gogh had a very heated argument with artist and friend Paul Gaugin. Gaugin left and Van Gogh, in a fit of anger and lunacy, severed his left earlobe with a razor.

Van Gogh wrapped his ear in a tissue and then went to a brothel, where he presented the ear to a prostitute. The next day the police found him and took him to a hospital. Gauguin refused to see him again.

Art historians Hans Kaufmann and Rita Wildegans think the Dutchman didn’t severe his own earlobe and that it was Gaugin who accidentally cut it with a sword either in anger or self-defence—Gauguin loved fencing and he has left his fencing mask and gloves in Van Gogh’s place in Arles, so their theory could be correct.

But whatever the real story, Van Gogh’s lack of ear is as popular as his art, and this 3D-printed copy of his severed earlobe is a huge deal for art lovers and pop culture aficionados.

The ear was grown at the Brigham and Women’s Hospital in Boston, in the US, and is kept alive inside a case that contains a special concoction that could make it last for a few years. It is on display at the Centre for Art and Media in Karlsruhe, Germany, and people can speak into it through a microphone.

“I use science basically like a type of brush, like Vincent used paint”, said Strebe to the Associated Press. The artist plans to exhibit the ear in New York too—we hope she brings it to Australia as well.

What would you tell Van Gogh?

VanGoghEar