For the first time, scientists have succeeded in growing empty particles derived from a plant virus and have made them carry useful chemicals.

The external surface of these nano containers could be decorated with molecules that guide them to where they are needed in the body, before the chemical load is discharged to exert its effect on diseased cells. The containers are particles of the Cowpea mosaic virus, which is ideally suited for designing biomaterial at the nanoscale.

“This is a shot in the arm for all Cowpea mosaic virus technology,” says Professor George Lomonosoff of the John Innes Centre, one of the authors on a paper to be published in Small.

Scientists have previously tried to empty virus particles of their genetic material using irradiation or chemical treatment. Though successful in rendering the particles non-infectious, these methods have not fully emptied the particles.

Scientists at the John Innes Centre discovered they could assemble empty particles from precursors in plants and then extract them to insert chemicals of interest. Scientists at JIC and elsewhere had also previously managed to decorate the surface of virus particles with useful molecules.

“But now we can load them too, creating fancy chemical containers,” says lead author Dr Dave Evans.

“This brings a huge change to the whole technology and opens up new areas of research,” says Prof Lomonossoff. “We don’t really know all the potential applications yet because such particles have not been available before. There is no history of them.”

One application could be in cancer treatment. Integrins are molecules that appear on cancer cells. The virus particles could be coated externally with peptides that bind to integrins. This would mean the particles seek out cancer cells to the exclusion of healthy cells. Once bound to the cancer cell, the virus particle would release an anti-cancer agent that has been carried as an internal cargo.

Some current drugs damage healthy cells as well as the cancer, leading to hair loss and other side effects. This technology could deliver the drug in a more targeted way.

“The potential for developing Cowpea mosaic virus as a targeted delivery agent of therapeutics is now a reality,” says Dr Evans.

Another weapon in the arsenal against cancer: Nanoparticles that identify, target and kill specific cancer cells while leaving healthy cells alone.

Led by Carl Batt, the Liberty Hyde Bailey Professor of Food Science, the researchers synthesized nanoparticles shaped something like a dumbbell made of gold sandwiched between two pieces of iron oxide. They then attached antibodies, which target a molecule found only in colorectal cancer cells, to the particles. Once bound, the nanoparticles are engulfed by the cancer cells.

To kill the cells, the researchers use a near-infrared laser, which is a wavelength that doesn’t harm normal tissue at the levels used, but the radiation is absorbed by the gold in the nanoparticles. This causes the cancer cells to heat up and die.

“This is a so-called ’smart’ therapy,” Batt said. “To be a smart therapy, it should be targeted, and it should have some ability to be activated only when it’s there and then kills just the cancer cells.”

The goal, said lead author and biomedical graduate student Dickson Kirui, is to improve the technology and make it suitable for testing in a human clinical trial. The researchers are now working on a similar experiment targeting prostate cancer cells.

“If, down the line, you could clinically just target the cancer cells, you could then spare the health surrounding cells from being harmed that is the critical thing,” Kirui said.

Gold has potential as a material key to fighting cancer in future smart therapies. It is biocompatible, inert and relatively easy to tweak chemically. By changing the size and shape of the gold particle, Kirui and colleagues can tune them to respond to different wavelengths of energy.

Once taken up by the researchers’ gold particles, the cancer cells are destroyed by heat just a few degrees above normal body temperature while the surrounding tissue is left unharmed. Such a low-power laser does not have any effect on surrounding cells because that particular wavelength does not heat up cells if they are not loaded up with nanoparticles, the researchers explained.

Using iron oxide which is basically rust as the other parts of the particles might one day allow scientists to also track the progress of cancer treatments using magnetic resonance imaging, Kirui said, by taking advantage of the particles’ magnetic properties.

A new method of growing arteries could lead to a “biological bypass” – or a non-invasive way to treat coronary artery disease, Yale School of Medicine researchers report with their colleagues in the April issue of Journal of Clinical Investigation.

Coronary arteries can become blocked with plaque, leading to a decrease in the supply of blood and oxygen to the heart. Over time this blockage can lead to debilitating chest pain or heart attack. Severe blockages in multiple major vessels may require coronary artery bypass graft surgery, a major invasive surgery.

“Successfully growing new arteries could provide a biological option for patients facing bypass surgery,” said lead author of the study Michael Simons, M.D., chief of the Section of Cardiology at Yale School of Medicine.

In the past, researchers used growth factors – proteins that stimulate the growth of cells – to grow new arteries, but this method was unsuccessful. Simons and his team studied mice and zebrafish to see if they could simulate arterial formation by switching on and off two signaling pathways – ERK1/2 and P13K.

“We found that there is a cross-talk between the two signaling pathways. One half of the signaling pathway inhibits the other. When we inhibit this mechanism, we are able to grow arteries,” said Simons. “Instead of using growth factors, we stopped the inhibitor mechanism by using a drug that targets a particular enzyme called P13-kinase inhibitor.”

“Because we’ve located this inhibitory pathway, it opens the possibility of developing a new class of medication to grow new arteries,” Simons added. “The next step is to test this finding in a human clinical trial.”

The thousands of bacteria, fungi and other microbes that live in our gut are essential contributors to our good health. They break down toxins, manufacture some vitamins and essential amino acids, and form a barrier against invaders. A study published in Nature shows that, at 3.3 million, microbial genes in our gut outnumber previous estimates for the whole of the human body. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, working within the European project MetaHIT and in collaboration with colleagues at the Beijing Genomics Institute at Shenzhen, China, established a reference gene set for the human gut microbiome a catalogue of the microbe genes present in the human gut. Their work proves that high-throughput techniques can be used to sequence environmental samples, and brings us closer to an understanding of how to maintain the microbial balance that keeps us healthy.

“Knowing which combination of genes is necessary for the right balance of microbes to thrive within our gut may allow us to use stool samples, which are non-invasive, as a measure of health,” says Peer Bork, whose group at EMBL took part in the analysis. “One day, we may even be able to treat certain health problems simply by eating a yoghurt with the right bacteria in it.”

This catalogue of the microbial genes harboured by the human gut will also be useful as a reference for future studies aiming to investigate the connections between bacterial genetic make-up and particular diseases or aspects of people’s lifestyles, such as diet.

To gain a comprehensive picture of the microbial genes present in the human gut, Bork and colleagues turned to the emerging field of metagenomics, in which researchers take samples from the environment they wish to study and sequence all the genetic material contained therein. They were the first to employ a high-throughput method called Illumina sequencing to metagenomics, dispelling previous doubts over the feasibility of using this method for such studies.

From a bacterium’s point of view, the human gut is not the best place to set up home, with low pH and little oxygen or light. Thus, bacteria have had to evolve means of surviving in this challenging environment, which this study now begins to unveil. The scientists identified the genes that each individual bacterium needs to survive in the human gut, as well as those that have to be present for the community to thrive, but not necessarily in all individuals, since if one species produces a necessary compound, others may not have to. This could explain another of the scientists’ findings, namely that the gut microbiomes of individual humans are more similar than previously thought: there appears to be a common set of genes which are present in different humans, probably because they ensure that crucial functions are carried out. In the future, the scientists would like to investigate whether the same or different species of bacteria contribute those genes in different humans.

In newborn mice, at least, mother’s milk appears to have some rather immediate and potentially far-reaching metabolic consequences. The milk intake kick-starts the liver to produce a molecule that then turns on heat-generating brown fat.

“A key phenomenon required after birth is to adapt the body to a lower environmental temperature with respect to that experienced when the fetus is inside the mother’s womb,” said Francesc Villarroya of the University of Barcelona. “We find that a key inducer of heat production in neonates is FGF21, released by the liver in response to the initiation of suckling.”

FGF21 (short for fibroblast growth factor 21) has recently emerged as a novel regulator of metabolism, Villarroya explained. Scientists knew that FGF21 is produced primarily in the liver, where it is induced after fasting in adult rodents and humans. FGF21 can also correct metabolic disorders of obese and diabetic mice.

In the new study, the researchers wanted to know whether FGF21 also has a role in metabolic shifts as newborn animals transition to life in the world. It appears that it does.

Plasma FGF21 levels and FGF21 gene expression in the liver rise dramatically after birth in mice, the researchers report. That increase is initiated by suckling and depends on the intake of lipid-rich milk. When the researchers mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, they found that the treatment enhanced the expression of genes involved in heat generation, or thermogenesis, within brown fat, to increase body temperature. Brown fat cells treated with FGF21 showed increased expression of thermogenesis genes. The cells also expended more energy and burned more glucose.

Villarroya’s team thinks what happens in those first hours of life may have consequences for the individual that carry over into adulthood, noting that FGF21 is a powerful antidiabetic agent.

“There are many evidences that alterations of dietary, genetic, environmental, or other origin in the metabolic performance during the fetal and early neonatal life can make an individual prone to develop diabetes and obesity in adulthood,” he said. “The precise mechanisms by which this happens are not fully understood. We observe that a ‘natural’ event in the postnatal life is a burst in FGF21 levels in response to suckling. It will be important to know whether any disturbance in the intensity of this naturally occurring event may have negative consequences in adulthood.”

Villarroya said that there has been something of a revolution in thinking about brown fat in recent years. That’s because scientists have found active brown fat in adult humans and have reported evidence that greater activity within brown fat can lend an individual greater resistance to obesity.

He says he suspects the pathways observed in neonatal mice do play similar roles in newborn humans, and maybe in adults, too. “It remains to be demonstrated if FGF21 is also an activator of brown fat in adult humans, but this would be of utmost importance for studies on complex metabolic diseases in adult humans,” he says.

Think back to your last fight with someone you love. How did you feel afterwards? How did you behave? Conflict with a loved one often leaves a person feeling terrible and then behaving badly. So much so that these scenarios have become soap opera clichés. After an argument, one partner may brood, slam the door, and then drive to a local bar to drown their sorrows in alcohol. These dramas rarely have happy endings. Given these stereotypes, how do people control their emotional reactions and prevent emotional storms and their attendant use of intoxicating substances?

A new study published in Biological Psychiatry, by Elsevier, suggests that the lateral prefrontal cortex (LPFC) is a brain region that may help people to control their emotional reactions to negative facial expressions from their romantic partners.

Christine Hooker and her colleagues recruited healthy, adult participants in committed relationships. The research subjects viewed positive, negative, and neutral facial expressions of their partners during a brain scan. In an online daily diary, participants reported conflict occurrence, level of negative mood, rumination, and substance use.

They found that LPFC activity in response to the laboratory-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to mood or behavior the next day. However, when an interpersonal conflict did occur, LPFC activity predicted mood and behavior the next day, such that lower activity was related to higher levels of negative mood, rumination, and substance use.

The study findings suggest that low LPFC function may be a risk-factor for mood and behavioral problems after a stressful interpersonal event.

The constructive management of negative emotional states that emerge inevitably within romantic relationships can be a critical facet of coping with the world. These relationships frequently serve as emotional havens from the stresses of the working world. Yet these relationships also may augment rather than reduce life stress. When that happens, problematic behaviors such as over-eating and substance abuse may increase.

Dr. John Krystal, Editor of Biological Psychiatry, commented on the importance of these findings: “When activated in the context of intense emotion, it appears that the LPFC helps us to manage the intensity of negative emotions that emerge in social relationships. When this brain region does not efficiently activate or when the intensity of the conflict is very high, people need to learn behavioral strategies to cope with the emotional response. For some people this strategy can be as simple as counting to 10 before doing something that they might regret later.”

This study raises an important question. How can clinicians enhance the function of the LPFC when its function is compromised? Cognitive and behavioral strategies may be important treatment components.

As Dr. Hooker explained, their findings “suggest that imaging can provide potentially useful information about who may be vulnerable to mood and behavioral problems after a stressful event. We hope that future research will build on this idea and explore ways that imaging can be used to inform people about their emotional vulnerabilities.”

Oxygen for ethanol oxidation is supplied through breathing, the stomach, and the skin. There is a great deal of genetic and environmental variability in the pharmacokinetics of alcohol absorption, distribution, metabolism, and elimination. A new study has found that increasing dissolved oxygen concentrations in alcohol may help to reduce alcohol-related side effects and accidents.
“Ethanol is oxidized to acetaldehyde, then further oxidized to water and carbon dioxide in the body after consumption,” explained Kwang-il Kwon, a professor in the college of pharmacy at Chungnam National University and corresponding author for the study. “These oxidation reactions occur primarily via hepatic oxidation and are governed by the catalytic properties of alcohol-metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH). Ethanol oxidation by ADH, ALDH, and MEOS requires oxygen, and a higher oxygen uptake increases the rate of ethanol oxidation.”

“Several studies have indicated that high-oxygen water can enhance the survival ability of mice, fatigue recovery, and anoxia endurance function,” added Hye Gwang Jeong, a professor in the department of toxicology in the college of pharmacy at Chungnam National University. “It can also increase energy storage. However, the influence of dissolved oxygen concentration on alcohol pharmacokinetics has not previously been described. This manuscript is the first to investigate the influence of dissolved oxygen concentrations on the pharmacokinetics of alcohol in healthy human subjects.”

Kwon and his colleagues performed three experiments with 49 healthy volunteers (30 men, 19 women), with a mean age of 27.2 years. Experiment one compared 8 ppm and 20 ppm dissolved oxygen concentrations in 240 ml of 19.5 percent alcoholic beverage. Experiment two compared 8 ppm and 20 ppm dissolved oxygen concentrations in 360 ml of 19.5 percent alcoholic beverage. Experiment three compared 8 ppm and 25 ppm dissolved oxygen concentrations in 360 ml of 19.5 percent alcoholic beverage.

Results showed that elevated, dissolved oxygen concentrations in alcoholic drinks can accelerate the metabolism and elimination of alcohol. For example, the time to reach 0.000 percent blood alcohol concentration (BAC) for the 240 ml of 19.5 percent alcoholic beverage with 20 ppm dissolved oxygen concentration was 20.0 min faster than with 8 ppm (257.7 min). The time to reach 0.000 percent BAC for the 360 ml of 19.5 percent alcoholic beverage with 20 ppm (334.5 min) and 25 ppm (342.1 min) dissolved oxygen concentration was 23.3 min and 27.1 min faster than with 8 ppm, respectively.

“The oxygen-enriched alcohol beverage reduces plasma alcohol concentrations faster than a normal dissolved-oxygen alcohol beverage does,” said Kwon. “This could provide both clinical and real-life significance. The oxygen-enriched alcohol beverage would allow individuals to become sober faster, and reduce the side effects of acetaldehyde without a significant difference in alcohol’s effects. Furthermore, the reduced time to a lower BAC may reduce alcohol-related accidents.”

Both Kwon and Jeong noted that alcoholic drinks with a higher oxygen concentration already exist in Korea, but they lack scientific support. “It seems that these drinks can maintain a high dissolved-oxygen concentration for about 10 to 20 days before the stopper is removed, and for 70 minutes after removing the stopper, respectively, at room temperature,” said Kwon.

The jumping gene or “Sleeping Beauty” transposon is “Molecule of the Year 2009″. This was announced by Professor Isidro T. Savillo, President of the International Society for Molecular and Cell Biology and Biotechnology Protocols and Researches (ISMCBBPR). The transposon was generated by Dr. Zsuzsanna Izsvák, Dr. Zoltán Ivics and Dr. Lajos Mátés of the Max Delbrück Center for Molecular Medicine in Berlin-Buch. According to the jury, it was selected out of 15 molecules nominated in the contest because “this molecule holds great promise for gene therapy”. The jury pointed out that it can stably transfer genes even to stem or progenitor cells and is safer than a viral vector. It is the first time that the Molecule of the Year has been awarded to major recipients outside the USA in Europe.

Transposable elements are molecular parasites that propagate themselves in genomes. But at the same time they provide plasticity to the genome that clearly contributed to the evolution of gene function across the tree of life. About half of the human genome is derived from ancient transposable element sequences.

However, due to mutations, the vast majority of the transposons became inactivated. Based on transposons in fish that are presumed to have been active approximately 20 million years ago, Dr. Ivics and Dr. Izsvák resurrected a jumping gene more than ten years ago. They named the transposon Sleeping Beauty, because they literally awakened it after a long evolutionary “sleep”.

The scientists modified the originally reconstructed transposon so that it acquired a highly elevated potency in gene transfer. In its award citation, the jury noted that this hyperactive transposon promises to be a revolutionary technology platform for genetic engineering in vertebrates.

Intelligent behavior requires strategic processing of numbers and abstract quantity information in accordance with internally maintained goals. For instance, we typically adopt a “less than” strategy when shopping for a product to pay the smallest amount of money. When searching for a job, on the other hand, our plan of action is “greater than”, and we strive to earn the largest sum of money. In such pragmatic situations, our decisions on quantities are guided by mathematical rules applied to them. They constitute the foundation of mathematical operations and are thus taught to first-graders. Neurobiologists in the laboratory of Andreas Nieder at the University of Tübingen now showed for the first time how brain cells process simple mathematical rules. The study is published online in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) (January 18.-24. 2010).

Humans are unrivalled in their understanding of numbers and rules, but the foundations of such high-level skills can already be found in the animal kingdom. To get a glimpse of where and how brain cells master such complex tasks, scientists at the Institute of Neurobiology in Tübingen trained rhesus monkeys to compare set sizes (numerosities) and to switch flexibly between two abstract mathematical rules. The “greater than” rule required the monkeys to release a lever if the first test display showed more dots than the sample display, whereas the “less than” rule required a lever release if the number of items in the test display was smaller compared to the first test display. The monkeys learned the quantitative “greater than/less than”-rule and were able to choose the smaller or greater set size relative to the sample numerosity, independently of the absolute numerosity of the displays. While the animals were performing this task, neurons recorded in the prefrontal cortex of the frontal lobe exhibited interesting activity. Irrespective of the absolute magnitude of the dot sets, the brain cells exclusively represented the mathematical rule at hand. Approximately one half of these neurons were only active whenever the animal followed the “greater than”-rule, whereas the other half preferred the “less than”-rule.

This new study provides valuable insight into the neurobiological foundations of highly abstract thinking that is necessary for mathematical operations. “First of all we want to understand how neurons process mathematical operations” Andreas Nieder explains. “At the same time, our investigations of the number sense are meaningful for assessing the very complex thinking processes that are necessary, for instance, when dealing with numbers.” It is the cerebral cortex at the frontal pole of the brain that constitutes the brain’s highest cognitive control center. This region of the brain also gives rise to mental activities that build personality. Damage to the frontal lobe (e.g. after injuries or stroke) disturb goal-directed logical thinking and reasoning. The new study provides important clues to how the healthy brain obeys abstract mathematical rules, which in turn will help to elucidate and treat related mental illnesses.

Bones, muscles and tendons work together to provide the perfect balance between stability and movement in the skeleton. Now, Weizmann Institute scientists show that this partnership begins in the embryo, when the bones are still taking shape. The study, published in a recent issue of Developmental Cell, describes a previously unrecognized interaction between tendons and bones that drives the development of a strong skeletal system.

‘Our skeleton, with its bones, joints and muscle connections serves us so well in our daily lives that we hardly pay attention to this extraordinary system,’ says Dr. Elazar Zelzer of the Weizmann Institute’s Molecular Genetics Department. ‘Although previous research has uncovered mechanisms that contribute to the development and growth of each component of this complex and wonderfully adaptable organ system, specific interactions between bones, muscles and tendons that drive the assembly of the musculoskeletal system are not fully understood.’

Zelzer, research student Einat Blitz, Sergey Viukov and colleagues, were interested in uncovering the molecular mechanisms that regulate the formation of bone ridges – bony protuberances that provide a stable anchoring point for the tendons that connect muscles with bones. Bone ridges are critical for the skeleton’s ability to cope with the considerable mechanical stresses exerted by the muscles. The researchers used embryonic mouse skeletons to study a bone ridge called the deltoid tuberosity, located on the humerus bone in the arm.

They discovered, to their surprise, that rather than being shaped by processes within the skeleton, bone-ridge formation was directly regulated by tendons and muscles in a two-phase procedure. First, the embryonic tendons initiated bone-ridge formation by attaching to the skeleton. This interaction induced the tendon cells to express a specific protein called scleraxis, which in turn, led to the production of another protein, BMP4 – a molecule involved in the onset of bone formation. Blocking BMP4 production in tendon cells prevented deltoid tuberosity bone ridge formation. In the second phase, the subsequent growth and ultimate size of the deltoid tuberosity was directly regulated by muscle activity.

The results demonstrate that tendons play an active role in initiating bone ridge patterning. Zelzer: ‘These findings provide a new perspective on the regulation of skeletogenesis in the context of the musculoskeletal system, and they shed light on an important mechanism that underlies the assembly of this system.’