In this cartoon, experimental magnetic beads are coated with human or pig mucins (grey mesh), which are proteins containing sialic acids (red or blue diamonds), part of a protective mucus net secreted by respiratory cells. Humans and pigs have different sialic acids on their mucins, as indicated by the bottom molecular structures. The flu virus (green stars) bind to and cleave off sialic acids, snipping through the host mucus net to infect cells.
Stuck on Flu
How a sugar-rich mucus barrier traps the virus – and it gets free to infect
Researchers at the University of California, San Diego School of Medicine have shown for the first time how influenza A viruses snip through a protective mucus net to both infect respiratory cells and later cut their way out to infect other cells.
The findings, published online today in Virology Journal by principal investigator Pascal Gagneux, PhD, associate professor in the Department of Cellular and Molecular Medicine, and colleagues, could point the way to new drugs or therapies that more effectively inhibit viral activity, and perhaps prevent some flu infections altogether.
Scientists have long known that common strains of influenza specifically seek and exploit sialic acids, a class of signaling sugar molecules that cover the surfaces of all animal cells. The ubiquitous H1N1 and H3N2 flu strains, for example, use the protein hemagglutinin (H) to bind to matching sialic acid receptors on the surface of a cell before penetrating it, and then use the enzyme neuraminidase (N) to cleave or split these sialic acids when viral particles are ready to exit and spread the infection.
Mucous membrane cells, such as those that line the internal airways of the lungs, nose and throat, defend themselves against such pathogens by secreting a mucus rich in sialic acids – a gooey trap intended to bog down viral particles before they can infect vulnerable cells.
Anthony Chetti is one of the beneficiaries of tractography-guided brain surgery. Chetti developed a tumor in the region of the brain called the occipital lobe, the portion of the brain responsible for processing visual information.
“Anytime that you are told that you can potentially lose your vision, you are scared,” said Chetti, a San Diego school teacher. “But when Dr. Chen shared the tractography images with me and showed me how he was going to avoid injury to the connection between my eye and the occipital lobe, I was reassured.”
Chetti underwent a complete excision of the brain tumor without any damage to his vision.
“When I woke up from surgery, I asked for my glasses immediately and began running systems checks. I could see the clock. I could read the words on a sign. It was immediately evident that there were no problems,” said Chetti.
Tractography scans can reveal tiny open paths between nerve fibers to reach brain tumors. The scans are color coded and display tiny neural connections. Other current imaging techniques such as computed tomography (CT) and conventional magnetic resonance imaging (MRI) cannot achieve this type of visual display.
UC San Diego neurosurgeons color code the brain with tractography - the circular object is a tumor.
Brain Surgeons Go with the Flow
Water-Based Imaging Technique Maps Brain Neurons Prior to Surgery
Neurosurgeons at UC San Diego Health System are using a new approach to visualize the brain’s delicate anatomy prior to surgery. The novel technique allows neurosurgeons to see the brain’s nerve connections thus preserving and protecting critical functions such as vision, speech and memory. No needles, dyes or chemicals are needed to create the radiology scan. The main imaging ingredient? Water.
“The brain can be mapped by tracking the movement of its water molecules,” said Clark Chen, MD, PhD, neurosurgeon and vice-chairman of neurosurgery at UC San Diego Health System. “Water molecules in brain nerves move in an oriented manner. However, outside the nerves, the molecules move randomly. Neurosurgeons at UC San Diego can use these distinct properties to locate important connections and to guide where surgery should occur or not.”
The technique, called tractography or diffusion tensor imaging (DTI), has been used for investigational and diagnostic purposes to better understand the effect of stroke and neurological diseases, such as Alzheimer’s. UC San Diego Health System neurosurgeons are among the first in the nation to apply this technology to guide brain tumor surgery.
“There are no margins for error in the brain. Every centimeter of brain tissue contains millions of neural connections so every millimeter counts,” said Chen. “With tractography, we can visualize the most important of these connections to avoid injury. In doing so, we will preserve the quality of life for our patients with brain cancer.”
Tongue bacteria. Image courtesy of Steve Gschmeissner
That’s a mouthful
This week, Rob Stein at NPR concluded his series on the human microbiome with a look at research investigating how our multitudinous intestinal bacteria may influence brain development and function. Turns out that old notion about “gut feelings” might have a biological basis.
These days, microbiome research is on everybody’s tongue, and thus the inspiration for today’s image: a colorized scanning electron micrograph of bacteria residing on a human tongue.
It should be no surprise that the human mouth is home to hundreds of microbial species. After all, it’s warm, moist and frequently open for business. It doesn’t start that way. A newborn has no bacteria in its oral cavity, but that soon changes – and changes even more as the mouth develops. Gums, cheeks and emerging teeth all provide distinct environmental niches for different bacterial species.
Some of these species are beneficial, aiding in digestion, for example. Many others are offer no direct benefit, but are helpful in occupying space that might otherwise be taken up by nastier bugs, such as those that cause tooth decay, periodontal diseases and worse. Poor oral hygiene has been linked to poor health elsewhere, including a higher risk of heart attack and cardiovascular disease.
Like fingerprints, everyone’s tongue is different. It’s the same with the assemblages of bacteria that call our mouths home. A recent microbial survey identified almost 400 different species in the mouths of 100 participants representing four different ethnic affiliations. Only 2 percent of the bacterial species were present in all of the individuals, albeit in different concentrations according to ethnicity. Eight percent were detected in 90 percent of the group. But most interestingly, said the researchers, each ethnic group – non-Hispanic blacks, whites, Chinese and Latinos – was identifiable by its own “signature” of shared microbes.
Image courtesy of the Alzheimer’s Reading Room
Don’t forget: Today is National Memory Screening Day
Everybody forgets stuff: Names, places, where they left their keys or what they ate for dinner last night. But as we age, these minor annoyances may become more worrisome:
Are they warning signs of Alzheimer’s disease?
No definitive test for Alzheimer’s disease currently exists. There are just clues. We asked Douglas Galasko, MD, a professor of neurosciences in the University of California, San Diego School of Medicine and director of the Shiley-Marcos Alzheimer’s Disease Research Center (ADRC) at UC San Diego, to talk about those clues and what the future holds.
Q: How does one differentiate the effects of normal aging, such as occasional forgetfulness, from dementia associated with diseases like Alzheimer’s?
A: Cognitive changes are an integral part of getting older. We become aware of lapses or glitches and often will blame them on ‘memory.’ However, not all of these changes are warnings of progressive memory failure and there are differences between the specific changes of aging and those linked to the early stages of Alzheimer’s disease.
People with Alzheimer’s disease have difficulty forming and retaining new memories, especially richly detailed memories of conversations and events. In the earliest stages, these may be intermittent and only present when someone tries to recall a more complex or novel event or a highly detailed conversation, but over time, the memory lapses become more consistent and pervasive. In contrast, age-related changes result in difficulty retrieving words or names (the tip-of-the-tongue phenomenon) and the word often will come back later. Aging also results in slowing of cognitive processing, greater vulnerability to being distracted and difficulty with multitasking. This can lead to losing one’s train of thought or not recalling something because we were distracted or not paying enough attention when we first heard it. When paying full attention, someone with age-associated symptoms should still be able to learn and recall new information well.
If I see someone in clinic who provides a richly detailed list of their memory failings and recalls specific incidents with great clarity, this suggests an age-associated or general medical problem. In contrast, when someone does not acknowledge or recall much about the specific problems that their concerned spouse or family members describe in detail, that is concerning for early Alzheimer’s disease.
Confocal image of an Alzheimer’s brain showing region of amyloid plaque. Courtesy of Wellcome Images.
Understanding a Protein’s Role in Familial Alzheimer’s Disease
Novel genomic approach reveals gene mutation isn’t simple answer
Researchers at the University of California, San Diego School of Medicine have used genetic engineering of human induced pluripotent stem cells to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer’s disease (AD), discovering that simple loss-of-function does not contribute to the inherited form of the neurodegenerative disorder.
The findings, published online in the journal Cell Reports, could help elucidate the still-mysterious mechanisms of Alzheimer’s disease and better inform development of effective drugs, said principal investigator Lawrence Goldstein, PhD, professor in the Departments of Cellular and Molecular Medicine and Neurosciences and director of the UC San Diego Stem Cell Program.
“In some ways, this is a powerful technical demonstration of the promise of stem cells and genomics research in better understanding and ultimately treating AD,” said Goldstein, who is also director of the new Sanford Stem Cell Clinical Center at UC San Diego. “We were able to identify and assign precise limits on how a mutation works in familial AD. That’s an important step in advancing the science, in finding drugs and treatments that can slow, maybe reverse, the disease’s devastating effects.”
Familial AD is a subset of early-onset Alzheimer’s disease that is caused by inherited gene mutations. Most cases of Alzheimer’s disease – there are an estimated 5.2 million Americans with AD – are sporadic and do not have a precise known cause, though age is a primary risk factor.
Hans von Gersdorff was one of Germany’s most noted surgeons during the late 15th and early 16th centuries, though little is known about the personal life or background of the man. He is best remembered for his illustrated Feldbuch der Wundartzney or Fieldbook of Surgery.
Based largely upon the writings of famed medieval surgeon Guy de Chauliac, Gersdorff’s tome was widely used as a basic surgical text for many years, most notably for its advice on limb amputation, which Gersdorff was reputed to be much experienced, with at least 200 procedures.
Feldbuch contained numerous woodcut images of surgical procedures, such as trephining and bone setting, anatomical schematics and diseases or medical conditions, such as leprosy. The woodcuts were done by Johann Ulrich Wechtlin.
Many of the images created by Gersdorff and Wechtlin were quite technical, if not always complete or precisely accurate. The image above, known as “Wound Man,” is likely intended to be more evocative in nature – a quick guide to injuries that military surgeons might see on a battlefield.
Gersdorff died in 1529 at the age of 74, presumably the consequence of old age and not from one of the mortal afflictions above.