In a laboratory at Michigan State University, scientists took a DIY approach to build a retrofitted cryo-electron microscope that allowed them to map a giant Samba virus -- one of the world's largest viruses.
"If the common cold virus is scaled to the size of a ladder, then the giant Samba virus is bigger than the Washington Monument," said Kristin Parent, assistant professor of biochemistry and molecular biology and co-author of the paper featured on the cover of the journal Viruses. "Cryo-EM allowed us to map this virus' structure and observe the proteins it uses to enter, or attack, cells."
It seems counterintuitive that bigger organisms are harder to see, but they are when using cryo-electron microscopy. That's because these microscopes usually are used to look at thin specimens and can't decipher larger organisms to reveal their biological mechanisms. For thick samples, scientists see only dark gray or black blobs instead of seeing the molecular framework.
Cryo-EM allowed Parent's team to image the giant Samba virus and understand the structures that allow it to enter an amoeba. Once inside, Samba opens one of its capsid layers and releases its nucleocapsid -- which carries the genetic cargo that sparks an infection. While Samba isn't known to cause any diseases in humans, its cousin, the mimivirus, may be a culprit for causing some respiratory ailments in humans.
"If you scoop up a handful of water from Lake Michigan, you are literally holding more viruses than there are people on the planet," said Parent, who published the paper with Jason Schrad and Eric Young, MSU biochemistry and molecular biology graduate students. "While scientists can't study every virus on Earth, the insights we glean from viruses like the giant Samba can help us understand the mechanisms of other viruses in its family, how they thrive and how we can attack them."
As bacteria become more resistant to antibiotics, looking for new ways to fight diseases will continue to grow in importance. Parent's lab also studies how bacteria-infecting viruses enter cells using this method, which could potentially lead to new antibacterial treatments. Yet the world's best cryo-EM microscope costs more than $5 million. Limited by funds but not drive, Parent was able to upgrade an existing microscope at MSU to do cryo-EM -- one that is a tinkerer's dream.
This traditional transmission electron microscope was retrofitted with a cryostage, which keeps viruses frozen in liquid nitrogen while they're being studied. Parent and her team then added a Direct Electron DE-20 detector, a powerful camera -- the mighty microscope's piece de resistance.
Parent didn't invent cryo-EM, but establishing it on campus serves as a viable proof-of-concept for MSU, opening the door for many interdisciplinary partnerships. This cutting-edge microscopy has applications across many fields, from those addressing a single protein to others studying entire cells. Virtually anyone studying complex molecular machines can advance their work with this tool, Parent added.
Parent has earned an AAAS Marion Milligan Mason Award for Women in the Chemical Sciences. This award, her paper in Viruses and being the co-author who performed cryo-EM work in a recent Nature Communications paper, lays the groundwork to some day have a more advanced cryo-EM microscope housed at MSU to be able to perform high-resolution structural studies.
"We've done quite a bit with our limited resources, but we're primed to do more," Parent said. "I think MSU could serve as a cryo-EM center and to increase the prevalence of this technology in the Midwest and beyond."
As one example, scientists from Universidade Federal de Minas Gerais (Brazil) and Universidade Federal do Rio de Janeiro (Brazil) also contributed to this study and benefitted from the technology MSU has to offer.
A study led by Ravi Bansal, PhD, and Bradley S. Peterson, MD, of The Saban Research Institute of Children's Hospital Los Angeles, has found structural differences in the cerebral cortex of patients with depression and that these differences normalize with appropriate medication. The study, published in Molecular Psychiatry on March 7, is the first to report within the context of a randomized, controlled trial, the presence of structural changes in the cerebral cortex during medication treatment for depression and the first to provide in vivo evidence for the presence of anatomical neuroplasticity in human brain.
"Our findings suggest that thickening of the cerebral cortex is a compensatory, neuroplastic response that helps to reduce the severity of depressive symptoms," said Peterson, director of the Institute of the Developing Mind at CHLA and professor of pediatrics and psychiatry at the Keck School of Medicine of the University of Southern California. "Patients off medication have a thickened cortex, and the thicker it is, the fewer the symptoms they have. Treatment with medication then reduces the severity of symptoms, which in turn reduces the need for biological compensation in the brain -- so that their cortex becomes thinner, reaching thickness values similar to those in healthy volunteers."
The investigators acquired anatomical brain scans at baseline and again at the end of the 10-week study period for 41 patients with chronic depression, while 39 healthy volunteers were scanned once. This study was conducted with adult patients treated at Columbia University, when Peterson and Bansal were faculty members.
Patients were randomized to receive active medication duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, or placebo. During the trial, patients receiving medication experienced significant improvement of symptoms compared with patients receiving placebo. In medication-treated patients, cortical thickness declined toward values found in healthy volunteers while placebo-treated patients showed a slight thickening of the cortex. According to Bansal, a researcher at CHLA and professor of pediatrics at the Keck School of Medicine of USC, this finding suggests that placebo-treated patients continue to require compensation for their ongoing symptoms.
"Although this study was conducted in adults, the methodology developed -- pairing a randomized controlled trial with MRI scanning -- can be applied to many other populations in both children and adults," said Bansal. "Also, our observations of neuroplasticity suggest new biological targets for treatment of persons with neuropsychiatric disorders."
Advanced technologies provide researchers with new insights into the warning signs for cardiovascular disease.
Screening methods for cardiovascular diseases such as heart attacks and strokes could be improved by measuring different biological signposts to those currently being tested, a new study led by researchers from King's College London suggests.
Published in the Journal of the American College of Cardiology, the study could allow doctors to better predict the development of cardiovascular disease at an earlier stage.
The research, which was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, explored the role of a family of proteins called apolipoproteins.
Currently, the main focus is on apolipoprotein A1 (apoA1), the main component of high-density lipoproteins (HDL) or 'good' cholesterol, and apolipoprotein B (apoB), which is present on low-density lipoproteins (LDL) or 'bad' cholesterol.
However, for the first time, researchers have used a technology called mass spectrometry to measure an unprecedented number of apolipoproteins in a population-based study and discovered that another group of apolipoproteins might complement the signposts of good and bad cholesterol: apoE, apoC2 and apoC3.
These apolipoproteins are associated with very low-density lipoproteins (VLDL) and predominantly linked to another type of fat called triglycerides. ApoE, apoC2 and apoC3 have shown a stronger association with cardiovascular disease than apoA1 and apoB, suggesting that currently some of the most predictive apolipoproteins are not measured in patients who may be at risk of cardiovascular disease.
The findings could lead to a change in the way patients all over the world are screened for cardiovascular disease, a condition which affects seven million people and causes more than 160,000 deaths in each year in the UK. It could also pave the way for more personalised treatments.
Lead author of the study Professor Manuel Mayr from King's College London said:
"We directly compared the association of a broad panel of apolipoproteins to new onset of cardiovascular disease over a 10-year observation period, and found that while apoB was predictive, other apolipoproteins, namely apoE, apoC2 and apoC3, were even better.
"These unexpected strong associations of VLDL-associated apolipoproteins with cardiovascular disease provide support to expanding the current measurements of apolipoproteins and to the concept of targeting additional apolipoproteins to reduce risk."
The study identified apoC3 as a prime therapeutic target for lowering VLDL, which might reduce excess cardiovascular risk related to high VLDL.
After all the lifting, hauling and wrapping, worn out gift givers may blame the season's physical strain for any shoulder soreness they are feeling. It turns out there could be another reason. A new study led by investigators at the University of Utah School of Medicine finds that individuals with symptoms that put them at increased risk for heart disease could be more likely to have shoulder problems, including joint pain and rotator cuff injury.
"If someone has rotator cuff problems, it could be a sign that there is something else going on. They may need to manage risk factors for heart disease," says the study's lead author Kurt Hegmann, M.D., M.P.H., Professor of Family and Preventive Medicine and Director of the Rocky Mountain Center for Occupational and Environmental Health. The research was published in the Journal of Occupational and Environmental Medicine.
Repeated physical stress is most frequently blamed for aggravating shoulder joints and the muscles and tendons that surround them. Think about a pitcher who throws a baseball 100 times a day. While physical exertion can certainly be an irritant, accumulating evidence points other factors that could also be at play. Previous research found that people who had an increased risk for heart disease also had a tendency toward carpal tunnel syndrome, Achilles tendinitis, and tennis elbow, all musculoskeletal disorders.
The current study by Hegmann and colleagues adds shoulder problems to the list and takes the connection one step further. The more heart disease risk factors that each of the study participants had racked up -- including high blood pressure, high cholesterol, diabetes -- the more likely they were to have had shoulder trouble.
36 participants with the most severe collection of risk factors were 4.6 times more likely than those with none of the risk factors to have had shoulder joint pain. They were also nearly six times more likely to have had a second shoulder condition, rotator cuff tendinopathy. Participants with mid-level heart risk were less likely to have had either shoulder condition, at 1.5 to 3-fold. Shared trends bolster that there could be a relationship between heart risk and shoulder problems, but researchers will need to follow up with a prospective study to prove cause and effect.
It may seem like physical strain would be at least just as likely to cause shoulder pain but data from the 1,226 skilled laborers who took part in the study suggest otherwise. Ergonomists carefully monitored airbag manufacturers, meat, processors, cabinet makers and skilled laborers. Every forceful twist, push, and pull was factored into a strain index assigned to each worker. But a more straining job did not translate to an uptick in shoulder difficulties. Nor did more time spent doing other physical activities.
"What we think we are seeing is that high force can accelerate rotator cuff issues but is not the primary driver," says Hegmann. "Cardiovascular disease risk factors could be more important than job factors for incurring these types of problems."
He says it's possible that controlling blood pressure and other heart risk factors could alleviate shoulder discomfort, too.
They said a rare few may live longer, but the odds were so poor you'd have to scour 10,000 planet Earths to find just one 125-year-old.
But while some scientists have praised the study, others have labelled it a dismal travesty.
Life expectancy has been increasing relentlessly since the nineteenth century - due to vaccines, safer childbirth and tackling killers like cancer and heart disease.
But can that go on forever?
The team in New York analysed data from the Human Mortality Database and the deaths of super-centenarians (those over 110) in France, Japan, UK and US.
The data showed increases in life expectancy were slowing in centenarians and that the maximum age of death had plateaued for at least two decades.
Prof Jan Vijg, one of the researchers from the Albert Einstein College of Medicine, told the BBC News website: "In people over 105 we make very little progress, that tells you we are most likely approaching the limit to human life.
"For the first time in history we've been able to see this, it looks like the maximum life span - this ceiling, this barrier - is about 115.
"It's almost impossible you'll get beyond it, you need 10,000 world's like ours to end up with one individual in a given year who will live until 125 - so a very small chance."
The oldest person
Jeanne Calment came close. The oldest ever person, whose age can be backed up by official documents, was 122 when she died in 1997.
The French icon of longevity was born before the Eiffel Tower was constructed and met the painter Vincent van Gogh.
Nobody has since got near her venerable age.
Prof Dame Linda Partridge, the director of the UCL Institute of Healthy Ageing, said a limit to lifespans "logically has to exist".
But she told the BBC: "Although this really interesting paper describes what is happening, it doesn't describe what will happen."
The crop of centenarians in the study were affected by malnutrition and infectious diseases in their childhood back in the late 19th Century. Remember smallpox was declared eradicated only in 1980.
"It was certainly very different to what the current birth cohort will go through, but it could yet be rather negative as a lot of children have grown up obese and that could bring lifespan down quite a lot," Prof Partridge added.
The 115-year claim is too much for Prof James Vaupel, the director of the Max Planck Institute for Demographic Research.
He described the study as a dismal travesty and said scientists had in the past claimed the limit was 65, 85 and 105 only to be proven wrong over and over again.
He said: "In this sorry saga, those convinced that there are looming limits did not apply demography and statistics to test hypotheses about lifespan limits—instead they exploited rhetoric, deficient methods and pretty graphics to attempt to prove their gut feelings.
"[This study] adds nothing to scientific knowledge about how long we will live."
Experiments, which look after animals in ideal conditions, have suggested lifespans do have a limit.
Prof Jay Olshansky, from the University of Illinois, said mice tend to live for about 1,000 days, dogs for about 5,000 days and "humanity is approaching a natural limit to life".
The challenge with tackling ageing is that we have not evolved to live to extreme old ages.
Millions of years of natural selection has honed us to survive, grow and reproduce in our youth.
What happens to our bodies half a century or more later - at ages we have never reached in our evolutionary history - are a side-effect of the instructions in our DNA that are important in youth.
So any attempt to really increase lifespan will need an approach that goes beyond treating diseases and tackles ageing inside every cell of the body.
Prof Jan Vijg added: "To get maximum life spans of 120, 125 or 130 maybe, we need to do something very fundamental here.
"We need to change the whole genetic make-up of the human species, you would have to develop thousands or tens of thousands of different drugs.
"The ageing process is so complicated that it will not be possible to substantially change this limit to human life."
The thread could be sewn into organs, wounds or orthopedic implants.
BOSTON, July 18 (UPI) -- The next time you have surgery, you may get sewn up with "smart" stitches.
Researchers at Tufts University have developed a new type of surgical thread capable of gathering diagnostic data and communicating it wirelessly in real time.
The development process allows scientists to integrate nano-scale sensors, electronics and microfluidics into a range of thread types -- something as basic as cotton or as complex as synthetics.
Once dipped in a series of sensory chemicals, the threads can measure the pressure, stress, strain and temperature inside a region of tissue. The smart threads can also measure pH and glucose levels. Such data can help doctors keep tabs on the healing process and alert caretakers to the early signs of infection.
The thread could be sewn into organs, wounds or orthopedic implants. The thread has yet to be tested in human patients, but it has revealed its potential in lab rats and test tube experiments.
Still, more research is needed to ensure the threads' biocompatibility.
"The ability to suture a thread-based diagnostic device intimately in a tissue or organ environment in three dimensions adds a unique feature that is not available with other flexible diagnostic platforms," researcher Sameer Sonkusale, director of the interdisciplinary Nano Lab at Tufts' School of Engineering, said in a news release. "We think thread-based devices could potentially be used as smart sutures for surgical implants, smart bandages to monitor wound healing, or integrated with textile or fabric as personalized health monitors and point-of-care diagnostics."