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Comment by Dr. Krishna Kumari Challa on August 26, 2015 at 6:00am

Universal flu vaccine is not far away...

Scientists from The Scripps Research Institute (TSRI) and the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) have found a way to induce antibodies to fight a wide range of influenza subtypes—work that could one day eliminate the need for repeated seasonal flu shots.

A yearly flu shot provides some protection from flu epidemics, subtypes not covered by the vaccine can emerge rapidly. This phenomenon was evident in the 2009 spread of the H1N1 (“swine flu”) subtype that killed an estimated 151,700 to 575,400 people worldwide.

In the last decade, several studies from TSRI, Janssen and other institutions have shown that some people are capable of making powerful antibodies that can fight many subtypes of influenza at once by targeting a site on the influenza virus that does not mutate rapidly. Unfortunately, these “broadly neutralizing antibodies,” or bnAbs, are rare.

Still, the tantalizing existence of broadly neutralizing antibodies led Janssen and TRSI to try creating an influenza vaccine specially designed to elicit them.

Researchers zeroed in on a possible target: a protein on the surface of influenza, called hemagglutinin (HA). HA is present on all subtypes of influenza, providing the key viral “machinery” that enables the virus to enter cells. Most importantly, the long “stem” region of HA, which connects the virus to cells, plays such a crucial role that mutations at the site are unlikely to be passed on. If the body can make an immune response against the HA stem, it’s difficult for the virus to escape.

To create antibodies against the HA stem, the research team looked to influenza’s own structure, specifically the universal recognition site of the broadly protective antibody CR9114 in the HA stem (described by Dreyfus et al., Science 2012). This vaccine candidate was designed, produced and tested by a team of scientists led by Jaap Goudsmit, head of the Janssen Prevention Center, the paper’s first author Antonietta Impagliazzo (responsible for the design) and co-senior author Katarina Radošević.

The effort represents the first time scientists have been able to cut off the variable head region of HA, designing features able to stabilize the conformation of the original protein, and at the same time faithfully mimicking the key broadly neutralizing site. The ultimate goal was to use this synthetic version of the HA stem in a vaccine to teach the body to make powerful antibodies against influenza virus, priming it to fight off a variety of flu strains.

The scientists then studied the response of rodent and nonhuman primate models given one of several candidate immunogens. They found that animals given one especially stable immunogen produced antibodies that could bind with HAs in many influenza subtypes, even neutralizing H5N1 viruses (“avian” or “bird” flu).

The reseaScientists at TSRI studied the structure of the immunogen at every point in the process. Using the imaging techniques of electron microscopy (led by TSRI Associate Professor Andrew Ward and postdoctoral fellow Ryan Hoffman) and x-ray crystallography (led by Wilson and TSRI Staff Scientist Xueyong Zhu), the team showed that the most promising candidate immunogen mimicked the HA stem and that antibodies could bind with the immunogen just as they would with a real virus.

With proof that an immunogen can elicit antibodies against the stem region, Wilson said the next step in this research is to see if the immunogen can do the same in humans.

The research was published online ahead of print on August 24 by the journal Science.

Source: Scripps Institute

Comment by Dr. Krishna Kumari Challa on August 25, 2015 at 8:27am

Scientists in countries affected by mosquito-borne diseases are less aware of the latest research on these diseases than those from countries where those diseases are not endemic, a study has found.

Diseases such as malaria and dengue fever are more prevalent in poorer countries, but these are also places where scientific communication is weaker and research institutions cannot afford access to journals and conferences, the study says. This leads to ignorance and widespread misconceptions about the state of research on the diseases mosquitoes transmit, which limits the ability of scientists from poorer countries to do ground-breaking work, the authors warn.

“Scientists from disease-endemic countries are not usually involved in the development of innovative biotech approaches against vector-borne diseases.”
The study was published in Parasites & Vectors on 10 August.
http://www.parasitesandvectors.com/content/8/1/414

Comment by Dr. Krishna Kumari Challa on August 25, 2015 at 6:45am

Dry air is heavier then wet air.

Yes, this fact sounds bit counterintuitive, and surprisingly the misconception of air getting "soaked with water" is widespread even between people who studied physics. Moreover, even some meteorology students often forget this.

It is not exactly new finding, but a centuries old one. At the same time, the explanation is quite easy - water molecules have lower molar weight than molecules of N2 O2 and few other gasses, and as a result the water vapour is less dense than dry atmospheric air. Therefore the wet air, which is essentially a mix of dry air with little bit of water vapour, is slightly less dense than the dry air of the same temperature.
Not like the difference is too big, but still significant enough to play vital role in formation of some storms, as well as those dangerous heatwaves.

At the same time, the misconception of air absorbing in water like a sponge is still widespread and probably would not change soon.

Comment by Dr. Krishna Kumari Challa on August 25, 2015 at 6:43am

Gamma-ray bursts (GRBs) are flashes of gamma rays associated with extremely energetic explosions that have been observed in distant galaxies. They are the brightest electromagnetic events known to occur in the universe. Bursts can last from ten milliseconds to several hours. The initial burst is usually followed by a longer-lived "afterglow" emitted at longer wavelengths (X-ray, ultraviolet, optical, infrared, microwave and radio).

Most observed GRBs are believed to consist of a narrow beam of intense radiation released during a supernova or hypernova as a rapidly rotating, high-mass star collapses to form a neutron star, quark star, or black hole. A subclass of GRBs (the "short" bursts) appear to originate from a different process – this may be due to the merger of binary neutron stars. The cause of the precursor burst observed in some of these short events may be due to the development of a resonance between the crust and core of such stars as a result of the massive tidal forces experienced in the seconds leading up to their collision, causing the entire crust of the star to shatter.
All GRBs observed to date have occurred well outside the Milky Way galaxy and have been harmless to Earth. However, if a GRB were to occur within the Milky Way, and its emission were beamed straight towards Earth, the effects could be devastating for the planet.
Depending on its distance from Earth, a GRB and its ultraviolet radiation could damage even the most radiation resistant organism known, the bacterium Deinococcus radiodurans. These bacteria can endure 2,000 times more radiation than humans. Life surviving an initial onslaught, including those located on the side of the earth facing away from the burst, would have to contend with the potentially lethal after-effect of the depletion of the atmosphere's protective ozone layer by the burst.
A Gamma ray burst can cause a mass extinction event anytime on Earth and we wont be able to do anything about it. We won't even see it coming !!!
A gamma ray burst (GRB) releases more energy in few seconds than that our sun will produce in its entire lifetime. Though these events are rare, astrophysicists think there is a 90 % chance that GRBs have caused at least one mass extinction event on Earth in the past.
Longer-term, gamma ray energy may cause chemical reactions involving oxygen and nitrogen molecules which may create nitrogen oxide then nitrogen dioxide gas, causing photochemical smog. The GRB may produce enough of the gas to cover the sky and darken it. Gas would prevent sunlight from reaching Earth's surface, producing a "cosmic winter" effect – a similar situation to an impact winter, but not caused by an impact. GRB-produced gas could also even further deplete the ozone layer.

Comment by Dr. Krishna Kumari Challa on August 25, 2015 at 6:20am

Human biology in general has some cool stuff that not many are aware of.

1. While the brain appears to be lacking any gross movement to the layman, the microglial cells in your brain have projections that sweep your brain and slurp up debris and what not. This is estimated to happen every few hours or so.

2. There is a gene called CLOCK (obviously) that plays a central role in regulating your circadian rhythm. Recent papers have even showed how this gene can regulate the functions of your immune cells.

3. You can now potentially sequence your genome for <1000 dollars. Or sequence the genome of a bacteria sitting at your home using a USB-powered device. 4. A new layer in the cornea called Dua layer was discovered as late as 2013. The discovery of this layer is now helping improve corneal surgeries and prevent rejections of corneal transplants. 5. Human retina has a million photoreceptors. Even if we only consider two possible states of existence (0/1), there are >1e300,000 possible bits of information. And this number is estimated to be beyong the Bremmermann's limit. Evolution has done a perfect job!

For more reading:

1. stanford.edu The brain’s silent majority: http://stanmed.stanford.edu/2009fall/article6.html
2. TH17 cell differentiation is regulated by the circad... [Science. 2013]
http://www.ncbi.nlm.nih.gov/pubmed?term=24202171
3. $1,000 genome https://en.wikipedia.org/wiki/$1,000_genome
4. USB stick can sequence DNA in seconds https://www.newscientist.com/article/dn21495-usb-stick-can-sequence...
5. Medscape: Dua Layer https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cDovL3d3...
6. Transcomputational problem https://en.wikipedia.org/wiki/Transcomputational_problem

Comment by Dr. Krishna Kumari Challa on August 25, 2015 at 5:44am

Some interesting things on trust:

What most people don't know is that trust can be something reasoned and actually has at least 12 properties. If all 12 of those properties can be verified positively you have close to 100% reason to trust. What we know is that the average person is content to trust with just 2 properties fulfilled and when drunk or in an emotional state, 1 property will suffice. There are tricks and fallacies which are perpetuated because they feel like they are fulfilling a trust property when they aren't. The two biggest fallacies perpetuated as trust reasons are transitive trusts (used in things like Amazon reviews) and Composability which has you trust based on majority (used in things like political speeches and "wisdom of crowds"). Now if you know this then you can protect yourself or you can manipulate others pretty well. So you can sell yourself on 1 trust property really well, like say Visibility, which shows your "transparency" and others think you are open about your motives or results then you can cheat like hell on the other 11 properties and scam your way through the populace.

There's details on this research in chapter 5 here: Open Source Security Testing Methodology Manual (OSSTMM) but there's new research coming out as this is 4 years old already. http://www.isecom.org/research/osstmm.html

Comment by Dr. Krishna Kumari Challa on August 25, 2015 at 5:36am

Here are some surprising findings on the neuro-science of perception:

1. The photoreceptors in the retina are activated by dark, not by light. (Visual phototransduction) https://en.wikipedia.org/wiki/Visual_phototransduction#In_the_dark
2. There are 10x more neural connections going backwards in the visual system than going forward (feedback vs. feedforward)* (Perception Lecture Notes: LGN and V1).
3. Human vision is so sensitive that it is possible to register a single photon. (Page on nyu.edu) http://www.cns.nyu.edu/~david/courses/perception/lecturenotes/V1/lg...
4. Human hearing is so sensitive that an eardrum displacement of 1 atom width can be heard. (Page on illinois.edu) https://courses.physics.illinois.edu/phys406/lecture_notes/p406pom_...
5. If a light flashes in the distance in the dark while your eye is moving, you will see it in the wrong place (Perisaccadic mislocalizaton: Page on sciencedirect.com). http://www.cell.com/neuron/abstract/S0896-6273%2803%2900003-5?_retu...
6. If you view colored objects in a room lit with "single frequency" light, all the colors disappear and everything looks gray. (Exhibit: Monochromatic Room) http://www.exploratorium.edu/visit/central-gallery/monochromatic-room
7. The tuning of neurons can be so specific that a neuron was found in one patient's hippocampus that responded to photos of Jennifer Aniston, but only when she was pictured without Brad Pitt. ** (Invariant visual representation by single neurons in the human brain) http://www.nature.com/nature/journal/v435/n7045/abs/nature03687.html

* This ratio only applies to the first stage of vision, from LGN to V1.
** This does not mean that the brain encodes information using "grandmother cells". See this paper by the authors of the study: Page on ucla.edu http://www.cnl.ucla.edu/CNL%20Publications/7.pdf

Comment by Dr. Krishna Kumari Challa on August 22, 2015 at 8:56am

Every year, more strains of bacteria develop resistance to the antibiotics we use to treat deadly infections. At The Scripps Research Institute (TSRI) scientists have been working to develop new forms of these drugs, including an antibiotic called arylomycin—but tests have shown that it is possible for bacteria to become resistant to arylomycin, too.

Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.

“This explains why antibiotic resistance rates in some bacteria are higher than in others,” said TSRI Professor Floyd Romesberg, senior author of the new study. “Resistance depends on this little set of genes that no one knew could contribute to tolerating the arylomycins.”

These findings were published this week by the journal mBio.
"An Alternative Terminal Step of the General Secretory Pathway in Staphylococcus aureus"
http://mbio.asm.org/content/6/4/e01178-15

Comment by Dr. Krishna Kumari Challa on August 22, 2015 at 8:52am

Treatments for the same opportunistic bacteria found in cystic fibrosis patients can work in one area in the lung and be less effective in others. The reason, reported August 20 in Cell Host & Microbe, is that bacteria become isolated from one another and evolve region-specific traits. Researchers saw differences in bacterial nutritional requirements, host defenses, and antibiotic resistance. The findings suggest that other chronic infections may yield similar bacterial diversity.

To understand how chronic bacterial infections persist in the face of antibiotics and immune defenses, researchers from the University of Washington School of Medicine dissected human lungs removed from patients with cystic fibrosis at the time of lung transplantation and collected thousands of one type of bacteria, pseudomonas, from different lung regions. The team found that while all of the pseudomonas in a lung were descendants of a single strain, each region contained a vast array of sibling bacteria that functioned differently.

"What made this so important to us is that the bacterial populations inhabiting different lung regions varied dramatically in terms of their antibiotic resistance and virulence," says lead author Dr. Peter Jorth. "This diversity could affect the patients' health."

When the investigators analyzed the genetic codes of the bacteria, the DNA sequences revealed that diversity arose because bacterial cells had become isolated in different lung regions and then evolved locally, much like Darwin's famed finches in the Galapagos.

The DNA sequences also suggest that traits that evolved over years or even decades may persist in bacteria inhabiting different lung regions and may provide a type of "memory" of past conditions and treatments that strengthen the bacteria.

"Even when a single strain of bacteria causes a chronic infection, evolution with human organs can produce diverse families of related bacteria," says senior author Dr. Pradeep Singh. "This may be part of what makes treatment so difficult, because when bacteria sensitive to one kind of stress are killed, functionally different siblings are there to take their place."

The researchers' next challenge is to use their understanding of how bacteria change during infection to find new ways to attack the diverse mixtures of bacteria that are present and to improve treatment for patients.
http://www.sciencedirect.com/science/article/pii/S193131281500298X
Bacteria Evolve Differences within the Lungs of Patients with Cystic Fibrosis

Comment by Dr. Krishna Kumari Challa on August 22, 2015 at 8:49am

Scientists have exposed a chink in the armour of disease-causing bugs, with a new discovery about a protein that controls bacterial defences. Bacteria react to stressful situations - such as running out of nutrients, coming under attack from antibiotics or encountering a host body’s immune system - with a range of defence mechanisms. These include constructing a resistant outer coat, growing defensive structures on their surface or producing enzymes that break down the DNA of an attacker.

The new research shows that a protein called sigma54 holds a bacterium’s defences back until it encounters stress, at which point the protein rearranges its structure to trigger the defences into action. The range of defences that sigma54 controls is so broad that the scientists are moving quickly to learn how to block its action and disable some of the bacteria's armour with new antibiotics.

The findings of the study are published recently in the journal Science by researchers at Imperial College London with collaborators at Peking University in China, Pennsylvania State University and University of Wisconsin-Madison, in the USA.

Structures of the RNA polymerase-s54 reveal new and conserved regulatory strategies. Yun Yang, Vidya C. Darbari, Nan Zhang, Duo Lu, Robert Glyde, Yiping Wang, Jared Winkelman, Richard L. Gourse, Katsuhiko S. Murakami, Martin Buck, Xiaodong Zhang. Science, 2015
Science news source:
Imperial College London

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