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Bacteriophages were discovered 100 years ago because of their ability to replicate in a pathogenic bacterium, kill it and thereby cure the patient. As a small spaceship landing on the moon, the microscopic particles land on the surface of the bacteria where they inject their deadly genetic material.
First author of the article, Heidi Gytz Olesen, Aarhus University
In fact, virus is nothing but small protein capsules enclosing the genetic material. The virus cannot replicate without a host cell, which it hijacks for its survival. During an infection, it utilises its host cell's metabolism to make lots of copies of the virus, which are subsequently released, and infect new host cells while the host cell dies.
An international team of researchers from Denmark and Russia used a series of biochemical and structural biology techniques to investigate how the Qβ bacteriophage, which infects the common coli bacteria, utilises several of its host cell's proteins while replicating its genetic material.
Immediately after infection, Qβ releases its genetic material into the host cell, where it is used as a template for the production of viral proteins. Qβ takes over the host cell's protein machine to synthesise its envelope proteins, as well as a virus-specific RNA polymerase, called a replicase. The task of the replicase is to replicate the virus' genetic material, whereas the host cell's genetic material is not to be recognised and copied. The replicase cannot cope with this task on its own, so it hijacks three 'helpers' from the host's own proteins namely the ribosomal protein S1, EF-Tu and EF-Ts, which all usually play important roles for the host cell's protein machine.
In a recently published work, the researchers have shown how ribosomal protein S1 plays a crucial role when the viral Qβ genetic material is to be distinguished from the genetic material of the coli bacteria prior to the replication process. Together, the replicase and S1 form a surface to which the viral genetic material is likely to bind during the recognition process. If this surface is mutated on the replicase, it loses its ability to accurately recognise the virus genome, which has fatal consequences for the virus, which can no longer replicate.
In the future, these findings may form the basis for the development of new methods for treating viral infections, as the majority of all virus faces a similar challenge, namely to have to selectively replicate its own genetic material in competition with the genetic material of the host cell. If this strategy fails, the virus will lose its ability to spread to new host cells and the infection will then be stopped.
The international research team consists of researchers from the Department of Molecular Biology and Genetics and the Interdisciplinary Nanoscience Center (iNANO), both from Aarhus University in Denmark, and from the Russian Academy of Sciences at Pushchino, Moscow, Russia.

News Source: Aarhus University 
Diacetyl, a flavoring chemical linked to cases of severe respiratory disease, was found in more than 75 percent of flavored electronic cigarettes and refill liquids tested by researchers at Harvard T.H. Chan School of Public Health.
Two other related, potentially harmful compounds were also found in many of the tested flavors, which included varieties with potential appeal to young people such as cotton candy, “Fruit Squirts,” and cupcake.
The study was published online today in Environmental Health Perspectives.
The Occupational Safety and Health Administration and the flavoring industry have warned workers about diacetyl because of the association between inhaling the chemical and the debilitating respiratory disease bronchiolitis obliterans, colloquially known as “popcorn lung” because it first appeared in workers who inhaled artificial butter flavor in microwave popcorn processing facilities.
“Recognition of the hazards associated with inhaling flavoring chemicals started with ‘popcorn lung’ over a decade ago. However, diacetyl and other related flavoring chemicals are used in many other flavors beyond butter-flavored popcorn, including fruit flavors, alcohol flavors, and, we learned in our study, candy-flavored e-cigarettes,” said lead author Joseph Allen, assistant professor of exposure assessment sciences.
There are currently more than 7,000 varieties of flavored e-cigarettes and e-juice (nicotine-containing liquid that is used in refillable devices) on the market. Although the popularity and use of e-cigarettes continues to increase, there is a lack of data on their potential health effects. E-cigarettes are not currently regulated, although the U.S. Food and Drug Administration (FDA) has issued a proposed rule to include e-cigarettes under its authority to regulate certain tobacco and nicotine-containing products.
Allen and colleagues tested 51 types of flavored e-cigarettes and liquids sold by leading brands for the presence of diacetyl, acetoin, and 2,3-pentanedione, two related flavoring compounds that the Flavor and Extract Manufacturers Association lists as “high priority,” i.e., they may pose a respiratory hazard in the workplace. Each e-cigarette was inserted into a sealed chamber attached to a lab-built device that drew air through the e-cigarette for eight seconds at a time with a resting period of 15 or 30 second between each draw. The air stream was then analyzed.
At least one of the three chemicals was detected in 47 of the 51 flavors tested. Diacetyl was detected above the laboratory limit of detection in 39 of the flavors tested. Acetoin and 2,3-pentanedione were detected in 46 and 23 and of the flavors, respectively.
“Since most of the health concerns about e-cigarettes have focused on nicotine, there is still much we do not know about e-cigarettes. In addition to containing varying levels of the addictive substance nicotine, they also contain other cancer-causing chemicals, such as formaldehyde, and as our study shows, flavoring chemicals that can cause lung damage,” said study co-author David Christiani, Elkan Blout Professor of Environmental Genetics.
Other Harvard Chan School authors included Skye Flanigan, Mallory LeBlanc, Jose Vallarino, Piers MacNaughton, and James Stewart.
This study was supported by an NIH/NIEHS Center grant.

Study Source: Harvard Gazette 
For bacteria that swim, determining whether to stay the course or head in a new direction is vital to survival. A new study offers atomic-level details of the molecular machinery that allows swimming bacteria to sense their environment and change direction when needed.
University of Illinois physics professor Klaus Schulten, right; physics graduate student Keith Cassidy, center; postdoctoral researcher Juan Perilla and their colleagues used experimental data and computer simulations to determine the structure of key regions of the “bacterial brain.” (Source: University of Illinois)

The study, reported in the journal eLife, represents a major step in understanding the "bacterial brain," said University of Illinois physics professor Klaus Schulten, who led the new research.
"On its surface, a bacterium has thousands of receptors that scan the environment and then tell it what to do," he said. This is very much like the sensory input that all animals must process. Of course, bacteria are single-celled organisms and don't have brains, he said. But they nonetheless manage to organize and "remember" sensory signals long enough to respond to them in a way that aids their own survival.
The receptors on the surface of a bacterial cell detect light, chemicals, edible things and poisonous things, and transmit that information to a deeper layer of proteins, called kinases, which interpret this data and translate it into a simple choice: "Keep going" or "Change direction!"
If the latter decision is made, a kinase hands off a potent chemical signal -- a phosphate -- to a second kinase, called CheY (KEY why), which then detaches, finds its way to the flagella and activates a process that causes the flagella to reverse their spin.
"That makes the bacterium tumble and go in a new, random direction, which may be better than the previous direction," Schulten said.
Previous studies have yielded key insights into the structure of the molecular machine that orchestrates this feat, the chemosensory array. Electron microscopy of the inner and outer surfaces of bacterial cells gives some clues, and crystallography -- a process that involves stacking purified proteins into crystals so that their three-dimensional characteristics can be measured -- provides others. But the fuzzy resolution of the EM snapshots leaves a lot of room for interpretation, and the crystals can resolve only small portions of the array's constituent proteins.
Study co-author, experimentalist Peijun Zhang of the University of Pittsburgh, aided this effort by developing a technique to purify the key proteins in the array and combine them in just the right proportions so that they assemble themselves in thin layers -- allowing clearer 3-D EM snapshots of their structural conformations and interactions with each other. This vastly improved the resolution of the data.
To resolve the picture of the chemosensory array, Schulten and his colleagues used molecular dynamic flexible fitting, a computer modeling approach Schulten's lab developed at Illinois. MDFF simulates the chemical interactions of every atom in a system and makes use of what is known about the structure from EM, crystallography and other experimental data. Such large-scale modeling and simulation requires the heft of a supercomputer, and for this effort the team used Blue Waters at the National Center for Supercomputing Applications at the U. of I.
The new study revealed key chemical interactions between the proteins that make up the chemosensory array, and offered new insights into the behavior of these proteins. For example, it revealed for the first time that one region of a kinase called CheA (KEY aye), changes its orientation in relation to the other proteins, in a motion the researchers call "dipping." Further experiments revealed that this part of the kinase is essential to the process that allows a bacterium to respond to its environment and change direction.
"A big question in the field is: How does the signal pass from the receptors to the kinases? What is actually happening?" Schulten said. "It has to be a motion. It can't be anything else. But what kind of motion?"
More work is needed to determine the relationships and behavior of all of the components of the system, but the new study represents a major gain in comprehension, Schulten said. He compares the process of discovery to that of someone encountering a mechanical clock for the first time.

"To know how this mechanical system works, we need to know the structure," he said. "Once we open the clock, see how the gears fit together, then we can start thinking about how the clock actually works. The gears of the bacterial brain are now in place."
Material Source: From Illinois News Bureau 
For a long time, bacteria were considered to be primitive structures, and it was not until the most modern of imaging techniques were used that their fine inner structure was discovered. The Berlin biophysicist Adam Lange has now succeeded in zooming in right up close: With the aid of a new technique of structural elucidation, he was able to show the basic building block of a bacterial skeleton down to atomic detail. The bactofilin investigated by his team only occurs in bacteria and may thus become a starting point for new antibiotics.
Bactofilin, discovered just five years ago, is found among other things in the bacterium Helicobacter pylori, which is responsible for the majority of gastric ulcers. Whereas it used to be thought that bacteria do not have a stabilising cytoskeleton, today we know that these microorganisms are in fact full of complex architectures, similar to the larger and in evolutionary terms more modern cells of plants and animals. Bactofilin gives Helicobacter pylori its typical screw-shaped form, thanks to which the bacterium can bore into the protective mucous layer of the inner wall of the stomach. The individual bactofilin molecules polymerise spontaneously in the interior of the bacteria to form the finest of fibres and higher order structures. An unusual structural motif plays a role here, as already discovered by the team of Adam Lange at the Leibniz-Institut für Molekulare Pharmakologie (FMP) in research work published at the beginning of this year. The proposed beta-helix fold had never before been found in a cytoskeleton. The bactofilin molecules are similar in form to spiral noodles with six twists, and in the process of polymerisation they accumulate together into long, extremely thin fibres.
The investigation of such fibre proteins is a challenge for structural biologists, as they can neither be dissolved in liquid nor can they be crystallised out, as is necessary for the commonly used methods. The two first authors of the paper, Chaowei Shi and Pascal Fricke, therefore used the relatively modern solid-state NMR, applying a new form of this technique further developed at the FMP that enables a particularly high resolution. NMR is the abbreviation for "nuclear magnetic resonance." It is based on the property of some atomic nuclei in a strong external magnetic field themselves to be turned into small magnets. On the basis of their characteristic resonance with radio waves, complicated calculation methods can be used to determine the position of the atoms within molecules. The special thing about solid-state NMR is that the sample is rotated very rapidly in the magnetic field in order to simulate the movements of dissolved molecules.
Since the exact form of the bactofilin building blocks and their chemical properties are now known, it is possible to search for small molecules that interfere with the polymerisation of the fibres. In this way, it might be possible to develop active substances that can specifically kill certain bacteria. The bactofilin fibres not only pass through the interior of Helicobacter -- in the harmless Caulobacter crescentus the fibres even form tightly interwoven mats. These mats are the foundation for a long stalk with which the bacteria can attach to surfaces or take up nutrients.
"All processes in living organisms are ultimately driven by proteins, and we have to know their structures in order to understand how they function," says Adam Lange. The biophysicist is one of the world's leading experts in the field of solid-state NMR, but in future he wants to push ahead with the combination of different techniques. "Impressive breakthroughs have also been achieved in the field of cryo-electron microscopy over the past few years, and we want to establish co-operations here," says Lange. "If one wants to understand protein structures in all their dimensions and details, experts must not work on their own in isolation, but rather we must integrate the modern powerful techniques into joint projects."

 Further Reading
C. Shi, P. Fricke, L. Lin, V. Chevelkov, M. Wegstroth, K. Giller, S. Becker, M. Thanbichler, A. Lange. Atomic-resolution structure of cytoskeletal bactofilin by solid-state NMRScience Advances, 2015; 1 (11): e1501087 DOI: 10.1126/sciadv.1501087
A group of researchers together from the University of Helsinki and the University of Edinburgh have been the first to find the genetic material of a human virus from old human bones. The research was published in the journal Scientific Reports, and the study analysed the skeletal remains of Second World War casualties from the battlefields of Karelia.
The researchers show that viral DNA is also present in bone
(Credit: Science Daily and 
University of Helsinki)

During the course of infection, allows virus to remain in the tissues, hence their DNA can be analyzed even after years thereafter. It has been common to find the genetic material in many organs but this time researchers have shown that viral DNA can also be present in bone.
"Human tissue is like a life-long archive that stores the fingerprint of the viruses that an individual has encountered during his or her lifetime," describes Klaus Hedman, professor of clinical virology.
The important implications behind the finding have open many gates of confusion since the current research unfolds the study of viruses that have caused infections in the past. The report published highlights the same. They document the presence of parvovirus DNA in the bones of Finnish World War II casualties who remained exposed to diverse climatic conditions in former Finnish, current Russian territory, until recent years when they were repatriated to their homeland. The study involved assessment of bone samples from 106 deceased, and the viral DNA was discovered in nearly half of them.
"By mapping and analysing the viral genes in old human samples, we can deepen our understanding of the way viruses develop and spread. The results can be compared to those with contemporary viruses and their virulence, improving our ability to prevent and eradicate infectious diseases," the scientists explain.
The DNA fingerprint
The bones of two of the casualties contained DNA from a type of parvovirus that has never circulated in the Nordic countries. This information, together with the human DNA profiles of these individuals, suggested that they were likely soldiers of the Red Army.
"Such a combination of human and viral DNA can help us both identify the recently dead -- making it a new tool for forensic identification or ancestry investigation- and determine how ancient humans migrated around the globe," states Antti Sajantila, Professor of genetic forensic medicine.
The virus- and forensic scientists of the University of Helsinki are determined to explore the viruses that existed centuries or even millennia ago and gave rise to ancient pandemics.
"It would be fascinating to find out what kinds of viruses were circulating in Mediaeval Europe, or how different were the viruses that existed among the populations of South America before the Europeans arrived."
The story derived from University of Helsinki

There are several efforts been made to investigate the association of fats in family background although several attempts well known to regulate by proper diet and exercise, but genetic insights may also help for proper prevention and treatment.
Harvard Medical Research investigators and MIT provides a majestic explanation behind the genetic association leading to obesity. The research was published in New England Journal of Medicine, reveals a major genetic circuit with new approach for obesity in patients.
Image Courtesy: Harvard Medical School

Earlier several attempts been made to identify how FTO gene associate with obesity. The risk for obesity behind these attempts was still vague to bring out the conclusive result. “Despite of investigating the FTO obesity region, no substantial expression differences were found between obesity-risk and non-risk individuals in brain or other tissue type, making it difficult to trace its mechanism of action,” said Manolis Kellis, professor of MIT’s CSAIL.
Researchers collected the adipose or fat tissue samples from patients with variant and also from non-variant control individuals; where they found distinct increased expressions of IRX3 and IRX5 genes by the risk variant. “We found a strong difference for both IRX3 and IRX5 genes in preadepocytes, revealing the target genes, cell type and developmental stage where the genetic variant acts, thus enabling us to begin dissecting its mechanism of action,” said Kellis.
To manipulate the exact role of these genes, the team inhibited the genes in the fat cells of mice. The result was majestic, since animals’ metabolism were increased and started losing weight although their physical activity and appetite were kept normal. “The results at the organism level were dramatic. These mice were 50 percent thinner than the control mice, and they did not gain any weight on a high-fat diet. Instead they dissipated more energy, even in their sleep, suggesting a dramatic shift in their global metabolism. Their circuitry underlying the FTO region functions like a master regulatory switch between energy storage and energy dissipation” said Melina Claussnitzer, an HMS instructor in medicine and an investigator in the Division of Gerontology at Beth Israel Deaconess and Hebrew Senior Life, a visiting professor at MIT’s Computer Science and artificial Intelligence Laboratory (CSAIL), and the member of Broad Institute.
The researchers then sought to connect the differences in metabolism and genetic differentiation between lean and obese people within FTO gene. They hypothesized that a single nucleotide variation from T to C in FTO gene may associate in obesity by repressing the conserved gene regulator ARID5B.
“Bidirectional genome editing of the casual nucleotide variant allowed us to demonstrate that a single nucleotide is responsible for flipping this metabolic switch between obese and lean individuals”, said Claussnitzer. She also added, “this is the first time that causality has been demonstrated for a genetic variant in a distal non-coding region, but we hope it will be first of many studies to come, now that genome editing is becoming broadly adopted”.
The story was adopted from the press release of Harvard Medical School.