Micro Eclectics

Even living cells have their own tangled problems to solve. They involve knots that arise accidentally in DNA and that can comprise its functionality. A new study by SISSA (Scuola Internazionale Superiore di Studi Avanzati) brings a new twist to the problem and suggests that the DNA propensity to be supercoiled, just like telephone cords, can come to the rescue. These coils can keep DNA knots locked in place for long enough that they can be untied by specialised enzymes. The computational study, based on molecular dynamics simulations of bacterial DNA, has just been published in Nucleic Acids Research . A tangled problem Supercoiled, twisted, and even knotted! Far from the elegant and polished textbook images, DNA filaments in living cells is all crumpled and entangled and, to be functional, needs to be constantly unravelled, much like our telephone cords that with careless use accumulate annoying curls or supercoils. "Supercoils are, in fact, present in DNA too

For bacteria facing a dose of antibiotics, timing might be the key to evading destruction. In a series of experiments, Princeton researchers found that cells that repaired DNA damaged by antibiotics before resuming growth had a much better chance of surviving treatment. When antibiotics hit a population of bacteria, often a small fraction of "persister" cells survive to pose a threat of recurrent infection. Unlike bacteria with genetic resistance to antibiotics, evidence suggests that persisters stay alive in part by stalling cellular processes targeted by the drugs. In a new study, Princeton researchers examined a class of antibiotics that target bacterial DNA. In bacterial populations, some cells repair damaged DNA before resuming growth, and others resume growth before making repairs. The researchers found that those that make repairs before resuming growth generally are the ones that survive as persisters. The research advances a long-term goal to make

Nanoparticles derived from tea leaves inhibit the growth of lung cancer cells, destroying up to 80% of them, new research by a joint Swansea University and Indian team has shown. The team made the discovery while they were testing out a new method of producing a type of nanoparticle called quantum dots. These are tiny particles which measure less than 10 nanometres. A human hair is 40,000 nanometres thick. Although nanoparticles are already used in healthcare, quantum dots have only recently attracted researchers' attention. Already they are showing promise for use in different applications, from computers and solar cells to tumour imaging and treating cancer. Quantum dots can be made chemically, but this is complicated and expensive and has toxic side effects. The Swansea-led research team were therefore exploring a non-toxic plant-based alternative method of producing the dots, using tea leaf extract. Tea leaves contain a wide variety of compounds, including

A study published in the BMJ Open journal shows that even moderate coffee consumption during pregnancy, one to two cups per day, is related to a risk of overweight or obesity in school age children. It has not been clearly shown if caffeine is the direct cause of the overweight, but the relationship, alone, has caused researchers to encourage increased caution. "There may be good cause to increase the restriction of the recommended maximum of three cups of coffee per day. Caffeine is not a medicine that needs to be consumed," says Verena Sengpiel, Associate Professor in obstetrics and gynecology at Sahlgrenska Academy, Sweden, and specialist physician at the Department of Obstetrics and Gynecology at Sahlgrenska University Hospital. Researchers at Sahlgrenska Academy, in collaboration with the Norwegian Institute of Public Health, studied information on 50 943 pregnant women, in one of the world's largest health surveys of pregnant women, the Norwegian

The HIV virus, which causes AIDS, has long been known to target and disable cells of the immune system, which are responsible for fighting off invading microorganisms and for suppressing malignant cancers. More recently, researchers also learned HIV not only targets immune cells in the bloodstream but also in the brain and spinal cord and that HIV can lie dormant in a person’s body for many years. My mentor, Dr. Habibeh Khoshbouei , has been working on this problem and learned that one consequence of HIV in the brain is that age-related diseases develop much earlier . This includes neurological conditions such as Alzheimer’s and Parkinson’s disease , as well as an increased susceptibility to drug addiction . Our lab wanted to learn why. HIV effects persist despite treatment HIV, the virus that causes AIDS, is shown budding out of an immune cell, which the virus infects and uses to replicate. NIH, via Wi

The real danger of separating children from parents is not the psychological stress – it’s the biological time bomb. The screaming and crying, the anguish and desolation is gut-wrenching. But the fallout pales in comparison to the less visible long-term effects that are more sinister and dangerous. Separating children from their parents, in a strange land, among strangers, causes the most extreme life stress a child can experience. And it causes profound and irreversible changes in how their DNA is packaged and which genes are turned on and off in the cells of the body, in organs like the pancreas, the lungs, heart and brain – leading to lifelong changes in its structure and function. I am the director of the Lieber Institute for Brain Development and the Maltz Research Laboratories at the Johns Hopkins University School of Medicine, where scientists study how genes and the environment shape the development of the human brain. Our studies and those of many other resea

Many of us may be considering “burning some fat” so we feel better in our bathing suits out on the beach or at the pool. What does that actually mean, though? The normal fat cell exists primarily to store energy. The body will expand the number of fat cells and the size of fat cells to accommodate excess energy from high-calorie foods. It will even go so far as to start depositing fat cells on our muscles, liver and other organs to create space to store all this extra energy from calorie-rich diets – especially when combined with a low activity lifestyle. Historically, fat storage worked well for humans. The energy was stored as small packages of molecules called fatty acids , which are released into the bloodstream for use as fuel by muscles and other organs when there was no food available, or when a predator was chasing us. Fat storage actually conferred a survival advantage in these situations. Those with a tendency to store fat were able to survive longer period

The unique composition of a mother’s breastmilk may help to reduce food sensitization in her infant, report researchers at the University of California San Diego School of Medicine with colleagues in Canada. The findings, publishing in the June 15 issue of Allergy , further highlight the health role of human milk oligosaccharides (HMOs), which are not found in infant formula, and underscore their potential for therapeutic interventions. HMOs are structurally complicated sugar molecules unique to human breast milk. They are the third most abundant solid component in human milk after lactose (a different type of sugar) and fat. They are not actually digestible by infants, but act as a prebiotic, helping to guide development of the infant gut microbiota, which previous research suggests is a key influencer of allergic disease. Past research has shown that breastfed infants have a lower risk for a variety of medical conditions, such as wheezing, infections, asthma and ob

Enterotoxigenic Escherichia coli (ETEC) is known as a major cause of diarrhea in travelers and people living in developing countries. According to the World Health Organization (WHO), ETEC is responsible for 300,000 ~ 500,000 deaths a year, constituting a serious problem. Effective vaccines for ETEC have not been developed, so patients infected with ETEC are treated with antibiotics and supporting measures. However, the emergence of multidrug-resistant bacteria has become a social issue, so the development of new treatment methods is sought after. Adherence to the host intestinal epithelium is an essential step for ETEC infection in humans. It was thought that a filamentous structure on the surface of bacteria called 'type IV pilus' was important for bacterial attachment, but its detailed adhesion mechanism was not known. Osaka University-led researchers clarified how pathogenic E.coli attached to the host intestinal epithelium using type IV pili and secre

With antibiotic resistance spreading worldwide, there is a strong need for new technologies to study bacteria. EMBL researchers have adapted an existing technique to study the melting behaviour of proteins so that it can be used for the study of bacteria. Molecular Systems Biology published their results -- allowing researchers worldwide to start using the technique -- on July 6. Thermal proteome profiling (TPP) was developed in 2014 (Savitski et al., Science 2014) and enables scientists to compare the melting behavior of all proteins in a cell or organism before and after a perturbation, such as the administration of a drug. By adapting TPP to bacteria, it can now be used to study the activity and architecture of most proteins in a bacterial cell while it's alive. André Mateus, a postdoc working in the Savitski and Typas groups at EMBL, led the study. Bacteria taking the heat While human bodies cease to function at temperatures above 42°C, E. coli bacteria st

Through x-ray crystallography and kinase-inhibitor specificity profiling, University of California San Diego School of Medicine researchers, in collaboration with researchers at Peking University and Zhejiang University, reveal that curcumin, a natural occurring chemical compound found in the spice turmeric, binds to the kinase enzyme dual-specificity tyrosine-regulated kinase 2 (DYRK2) at the atomic level. This previously unreported biochemical interaction of curcumin leads to inhibition of DYRK2 that impairs cell proliferation and reduces cancer burden. But before turning to curcumin or turmeric supplements, Sourav Banerjee, PhD, UC San Diego School of Medicine postdoctoral scholar, cautions that curcumin alone may not be the answer. "In general, curcumin is expelled from the body quite fast," said Banerjee. "For curcumin to be an effective drug, it needs to be modified to enter the blood stream and stay in the body long enough to target the cancer.

Scientists from UNSW Sydney and the UK have discovered that the human immunodeficiency virus (HIV) hijacks a small molecule from the host cell to protect itself from being destroyed by the host's immune system. The finding, as well as details of the new strategy that enabled it, are published as back-to-back papers in eLife. They identify a new target for antiviral therapy against HIV and provide a method for testing and measuring new drugs designed to target the capsid. UNSW PhD student Chantal Márquez is involved in both studies and is the first author of the paper describing the new method. HIV forms a protein shell -- called a capsid -- that shields its genetic material from host defence mechanisms as it enters the cell and makes its way to the nucleus to establish infection. Using a new single-molecule microscopy technique -- developed at UNSW's Single Molecule Science in the Faculty of Medicine -- the research teams found that HIV specifically incorpor

The bacteria that cause the devastating disease tuberculosis have the ability to escape destruction and grow after they are engulfed by lung macrophages, the immune cells that are supposed to destroy pathogens. Now researchers at the University of Alabama at Birmingham have described key biochemical steps between the bacteria Mycobacterium tuberculosis and the macrophage responsible for that ability. This knowledge, Michael Niederweis, Ph.D., and colleagues say, reveals patient-targeted strategies to treat tuberculosis, which kills 1.4 million people and infects another 10 million each year. Niederweis is a professor of microbiology at UAB, and the study appears in the journal Cell Reports . Three years ago, the Niederweis group described the first toxin ever found in M. tuberculosis despite 132 years of study. This contrasted with nearly all other pathogenic bacteria, whose toxins contribute to illness or death. They named the toxin tuberculosis necrotizing toxin,

Many of society’s energy challenges require gigawatts of power , but many more are small – and some are entirely microscopic. To drive a new generation of tiny micromachines that could deliver drugs or clean traces of pollution , physicists are increasingly looking to biology for inspiration. In work published in the journal Science Advances , my co-authors and I present a simulation of a sort of tiny “windfarm” powered by the natural self-organisation of bacteria. It’s a small step towards harnessing the energy potential of microorganisms. Active fluid-powered windfarms We used computer simulations to model many swimming bacteria, such as the E. coli you find in your gut. A dense crowd of these swimming bacteria isn’t too different from traditional, passive liquid, though there’s one major exception: it spontaneously flows, with internal whirling currents. Physicists have started calling anything that spontaneously flows in this way an “ active fluid ”. It looks som

Researchers have found an association between migraines and microbes that reduce nitrates. Analyzing data from the American Gut Project, they found that migraine sufferers harbored significantly more microbes in their mouths and guts with the ability to modify nitrates compared to people who do not get migraine headaches. Many of the 38 million Americans who suffer from migraines have noticed an association between consuming nitrates and their severe headaches. Nitrates, found in foods like processed meats, green leafy vegetables, and in certain medicines, can be reduced to nitrites by bacteria found in the oral cavity.  About 80% of cardiac patients who take nitrate-containing drugs for chest pain or congestive heart failure report severe headaches as a side effect. The researchers speculate that we may have a symbiotic relationship with our oral microbes, which aids our cardiovascular health, or that too many nitrate-reducing bacteria in the mouth may also lead to migr

Bacteria have an immune system to fight off invasive viruses called phages, and like any immune system, from single-celled to human, the first challenge of the bacterial immune system is to detect the difference between “foreign” and “self.” Since all living things are made of DNA and proteins, how do viruses and bacteria recognize their own? “In most environments, phages are around ten times more abundant than bacteria. And, like all viruses, phages use the host cell’s replication machinery to make copies of themselves,” says Prof. Rotem Sorek of the Weizmann Institute’s Department of Molecular Genetics. “And they are constantly evolving new ways to do this. So bacteria need a very active immune system to survive.” But until recently, scientists were not even sure that bacteria had an adaptive immune system – one that “remembers” a past encounter to produce a targeted response. That changed several years ago when a bacterial adaptive system called CRISPR was discovered.

One reason we're supposed to eat a variety of colorful fruits and vegetables is because they contain nutritious compounds called antioxidants. These molecules counteract the damage to our bodies from harmful products of normal cells called reactive oxygen species (ROS). Now, research led by a Salk Institute professor along with collaborators from Yale, Appalachian State University and other institutions found that a protein called ATM (short for ataxia-telangiectasia mutated) can sense the presence of ROS and responds by sounding the alarm to trigger the production of antioxidants. The work, which appears in Science Signaling on July 10, 2018, could have implications for a disease in which ATM is dysfunctional -- and could also help reveal ways to boost cellular health overall. "In ataxia-telangiectasia, the disease caused when the ATM is gene is mutated, people are prone to DNA damage because one of ATM's functions is to repair DNA," says Salk

Modern life can be stressful and the effects of environmental stressors on the mind have been a topic of interest in recent times. However, how much do we know of how our environmental stress affects our bodies? The research area of autophagy focusses on the mechanisms our cells have evolved to combat stressful conditions: such as lack of nutrition, infection or excess damage caused by daily activities. In this, we showcase some of our best papers within the area of autophagy to highlight how the field has grown in the last decade. Human beings have augmented their waste recycling efforts in the recent decades, however our cells have always had tightly regulated processes that facilitate nutrient recycling and removal of cellular damage in times of stress. One of these processes, known as “autophagy” was first observed and named by the Belgian scientist Christian de Duve in the 1950s. While studying the effects of insulin on rat liver, de Duve accidentally discover

Research by a team led by Dr Elizabeth Fullam, has revealed new findings about an enzyme found in Mycobacterium tuberculosis (Mtb) the bacterium that causes TB. TB causes more deaths than any other infectious disease, including from HIV and malaria. In 2016 there were 10.4 million new cases of TB and 1.7 million people died. The rise in cases of TB that are resistant to the current therapies that are available means that there is an urgent need to develop new TB therapeutics. Mtb is a highly unique bacterium and is enclosed within a distinctive cell wall that is comprised of unusual sugars and lipids which protect the bacteria from the host environment. Disruption of essential pathways involved in the assembly of the Mtb cell wall is an attractive approach for new TB drugs. The team found a key structural motif in the tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA) enzyme. Attacking this structural motif through the design and exploitation of new mol

Researchers at Carnegie Mellon University and Yale University have for the first time used a gene editing technique to successfully cure a genetic condition in a mouse model. Their findings, published in Nature Communications , present a promising new avenue for research into treating genetic conditions during fetal development. An estimated 8 million children are born each year with severe genetic disorders or birth defects. Genetic conditions can often be detected during pregnancy using amniocentesis, but there are no treatment options to correct these genetic conditions before birth. "Early in embryonic development, there are a lot of stem cells dividing at a rapid pace. If we can go in and correct a genetic mutation early on, we could dramatically reduce the impact the mutation has on fetal development or even cure the condition," said Danith Ly, professor of chemistry in Carnegie Mellon's Mellon College of Science. In this study, the researchers use

Transport proteins called efflux pumps, and their role in creating drug-resistance in bacteria, could lead to improving effectiveness of drugs against life-threatening diseases and perhaps even bring defunct antibiotics back to prominence. Some life-threatening infections do not respond to antibiotics because efflux pumps inside a particular type of infectious microbe called Gram-negative bacteria flush out antibiotics before the drugs can work. One type of efflux pump, which until recently had only been studied in parts, was recently modeled in its entirety and simulated using supercomputers at Los Alamos National Laboratory. The findings offer a better understanding of the motions and functions of efflux pumps . The work exploits the Laboratory’s extensive modeling and supercomputing simulation capabilities developed in support of its national security mission. For this study, the researchers focused on efflux pumps inside the bacteria Pseudomonas aeruginosa, which