Tag Archives: human health

Researchers Find Switch That Allows Cancer Cells to Spread

Researchers discovered of a specific protein called disabled-2 (Dab2) that switches on the process that releases cancer cells from the original tumor and allows the cells to spread and develop into new tumors in other parts of the body.

The process called epithelial-mesenchymal transdifferientiation (EMT) has been known to play a role in releasing cells (epithelial cells) on the surface of the solid tumor and transforming them into transient mesenchymal cell: cells with the ability to start to grow a new tumor.

This is often the fatal process in breast, ovarian, pancreatic and colon-rectal cancers.

Searching to understand how the EMT process begins, Ge Jin, who has joint appointments at the Case Western Reserve University School of Dental Medicine and the Lerner Research Institute at the Cleveland Clinic, began by working backwards from EMT to find its trigger. The researchers found that a compound called transforming growth factor-ÃŸ (TGF-ÃŸ) triggers the formation of the Dab2 protein. It was this protein, Dab2, that activated the EMT process.

He discovered that when the researchers knocked out Dab2, EMT was not triggered. “This is the major piece in cancer research that has been missing,” Jin said. Most tumors are epithelial in origin and have epithelial markers on their surface. The EMT process takes place when some of those cells dislodge from the surface and undergo a transformation into a fibrous mesenchymal cell maker with the ability to migrate.

“EMT is the most important step in this process,” said Jin. He was part of a six-member research team, led by Philip Howe from the Department of Cancer Biology at the Lerner Research Institute in a National Institute of Cancer-funded study. The research group studied the biological processes that initiated the cancer spread by using cancer cells in animal models.

“If we can understand the signaling pathway for modulating EMT, then we can design drugs to delay or halt EMT cells and control tumor progression,” Jin said. Beyond cancer, Jin said. “The process we discovered may lead to understanding how other diseases progress.”

Microbes Flourish In Healthy People

Bugs Inside: What Happens When the Microbes That Keep Us Healthy Disappear? by Katherine Harmon

The human body has some 10 trillion human cells—but 10 times that number of microbial cells. So what happens when such an important part of our bodies goes missing?
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“Someone who didn’t have their microbes, they’d be naked,” says Martin Blaser, a professor of microbiology and chair of the Department of Medicine at New York University Langone Medical Center in New York City.
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Even though it is such an apparently integral and ancient aspect of human health, scientists are still grasping for better ways to study human microbiota—before it changes beyond historical recognition. Borrowing models from outside of medicine has helped many in the field gain a better understanding of this living world within us. “The important concept is about extinctions,” Blaser says. “It’s ecology.”
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The first step in understanding these systems is simply taking stock of what archaea, bacteria, fungi, protozoa and viruses are present in healthy individuals. This massive micro undertaking has been ongoing since 2007 through the National Institutes of Health’s (NIH) Human Microbiome Project. So far it has turned up some surprisingly rich data, including genetic sequencing for some 205 of the different genera that live on healthy human skin.

Despite the flood of new data, Foxman laughs when asked if there is any hope for a final report from the Human Microbiome Project any time soon. “This is the very, very beginning,” she says, comparing this project with the NIH’s Human Genome Project, which jump-started a barrage of new genetic research. “There are basic, basic questions that we don’t know the answers to,” she says, such as how different microbiota are between random individuals or family members; how much microbiota change over time; or how related the microbiota are to each other on or inside a person’s body.

Printing Bone, Muscle and More

A Pittsburgh-based research team has created and used an innovative ink-jet system to print “bio-ink” patterns that direct muscle-derived stem cells from adult mice to differentiate into both muscle cells and bone cells.

The custom-built ink-jet printer, developed at Carnegie Mellon’s Robotics Institute, can deposit and immobilize growth factors in virtually any design, pattern or concentration, laying down patterns on native extracellular matrix-coated slides (such as fibrin). These slides are then placed in culture dishes and topped with muscle-derived stem cells (MDSCs). Based on pattern, dose or factor printed by the ink-jet, the MDSCs can be directed to differentiate down various cell-fate differentiation pathways (e.g. bone- or muscle-like).

“This system provides an unprecedented means to engineer replacement tissues derived from muscle stem cells,” said Johnny Huard, professor of orthopedic surgery at the University of Pittsburgh School of Medicine and director of the Stem Cell Research Center at Children’s Hospital of UPMC. Huard has long-standing research findings that show how muscle-derived stem cells (MDSCs) from mice can repair muscle in a model for Duchenne Muscular Dystrophy, improve cardiac function following heart failure, and heal large bone and articular cartilage defects.

Weiss and Campbell, along with graduate student Eric Miller, previously demonstrated the use of ink-jet printing to pattern growth factor “bio-inks” to control cell fates. For their current research, they teamed with Phillippi, Huard and biologists of the Stem Cell Research Center at Children’s Hospital to gain experience in using growth factors to control differentiation in populations of MDSCs from mice.

The team envisions the ink-jet technology as potentially useful for engineering stem cell-based therapies for repairing defects where multiple tissues are involved, such as joints where bone, tendon, cartilage and muscle interface. Patients afflicted with conditions like osteoarthritis might benefit from these therapies, which incorporate the needs of multiple tissues and may improve post-treatment clinical outcomes.

The long-term promise of this new technology could be the tailoring of tissue-engineered regenerative therapies. In preparation for preclinical studies, the Pittsburgh researchers are combining the versatile ink-jet system with advanced real-time live cell image analysis developed at the Robotics Institute and Molecular Biosensor and Imaging Center to further understand how stem cells differentiate into bone, muscle and other cell types.

Prion Proteins, Without Genes, Can Evolve

‘Lifeless’ prion proteins are ‘capable of evolution’

scientists transferred prion populations from brain cells to other cells in culture and observed the prions that adapted to the new cellular environment out-competed their brain-adapted counterparts. When returned to the brain cells, the brain-adapted prions again took over the population.

Charles Weissmann, head of Scripps Florida’s department of infectology who led the study, said: “On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses.

“This means that this pattern of Darwinian evolution appears to be universally active. “In viruses, mutation is linked to changes in nucleic acid sequence that leads to resistance.

“Now, this adaptability has moved one level down- to prions and protein folding – and it’s clear that you do not need nucleic acid (DNA or RNA) for the process of evolution.”
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He said: “The prion protein is not a clone, it is a quasi-species that can create different protein strains even in the same animal. “The abnormal prion proteins multiply by converting normal prion proteins.

“The implication of Charles Weissmann’s work is that it would be better to cut off that supply of normal prion proteins rather than risk the abnormal prion adapting to a drug and evolving into a new more virulent form.

Microcosm by Carl Zimmer

cover of Microcosm by Carl Zimmer

Microcosm: E. Coli and the New Science of Life by Carl Zimmer is an excellent book. It is full of fascinating information and as usual Carl Zimmer’s writing is engaging and makes complex topics clear.

E-coli keep the level of oxygen low in the gut making the resident microbes comfortable. At any time a person will have as many as 30 strains of E. coli in their gut and it is very rare for someone ever to be free of E. coli. [page 53]

In 1943, Luria and Delbruck published the results that won them the 1969 Nobel Prize in Physiology or Medicine in which they showed that bacteria and viruses pass down their traits using genes (though it took quite some time for the scientific community at large to accept this). [page 70]

during a crisis E coli’s mutation rates could soar a hundred – or even a thousandfold… Normally, natural selection favors low mutation rates, since most mutations are harmful. But in times of stress extra mutations may raise the odds that organisms will hit on a way out of their crisis… [alternatively, perhaps] In times of stress, E coli. may not be able to afford the luxury of accurate DNA repair. Instead, it turns to the cheaper lo-fi polymerases. While they may do a sloppier job, E coli. comes out ahead [page 106]
Hybridization is not the only way foreign DNA got into our cells. Some 3 billion years ago our single-celled ancestors engulfed oxygen-breathing bacteria, which became the mitochondria on which we depend. And, like E. coli, our genomes have taken in virus upon virus. Scientists have identified more than 98,000 viruses in the human genome, along with our mutant vestiges of 150,00 others… If we were to strip out all our transgenic DNA, we would become extinct.

I highly recommend Microcosm, just as I highly recommend Parasite Rex, by Carl Zimmer.

Disrupting Bacterial Communication to Thwart Them

Interrupting Bacterial Chatter to Thwart Infection

To measure their own numbers, bacteria produce, release, and detect chemical signals called autoinducers. As a population of bacteria grows, it releases more autoinducer into its environment. When individuals detect that a threshold level of autoinducer is present, they change their behavior – by releasing a toxin, for example.

Bassler and her colleagues disrupted these lines of communication by interfering with molecules called acyl-homoserine lactone (AHL) autoinducers, which drive quorum sensing among a kind of bacteria known as Gram-negative bacteria. Gram-negative bacteria include Pseudomonas, E. coli and Salmonella, and other disease-causing microbes. In the study, the team focused on Chromobacterium violaceum, which rarely infects human, but can be lethal to other organisms. C. violaceum lends itself to studies of quorum sensing because it produces a readily detected, bright purple dye when it detects that its population has reached a critical mass.
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The experiment shows that interfering with quorum sensing may provide an alternative to traditional antibiotics, Bassler says, and circumvent the problem of resistance that antibiotics foster by killing off susceptible bacteria but allowing resistant ones to survive and propagate.

Re-engineering the Food System for Better Health

Good food nation

According to the Centers for Disease Control, between 1980 and 2006 the percentage of obese teenagers in the United States grew from 5 to 18, while the percentage of pre-teens suffering from obesity increased from 7 to 17.
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Obesity is widespread due to our national-scale system of food production and distribution, which surrounds children – especially lower-income children – with high-calorie products…
90 percent of American food is processed – according to the United States Department of Agriculture – meaning it has been mixed with ingredients, often acting as preservatives, that can make food fattening.
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Now, in another report finished this October after meetings with food-industry leaders, the MIT and Columbia researchers propose a solution: America should increase its regional food consumption.
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Only 1 to 2 percent of all food consumed in the United States today is locally produced. But the MIT and Columbia team, which includes urban planners and architects, believes widespread adoption of some modest projects could change that, by increasing regional food production and distribution.

To help production, the group advocates widespread adoption of small-scale innovations such as “lawn to farm” conversions in urban and suburban areas, and the “10 x 10 project,” an effort to develop vegetable plots in schools and community centers. Lawns require more equipment, labor and fuel than industrial farming nationwide, yet produce no goods. But many vegetables, including lettuce, cucumbers and peppers, can be grown efficiently in small plots.
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As Albright sees it, the effort to produce healthier foods “fits right in with the health-care reform effort right now because chronic diseases are so costly for the nation.” America currently spends $14 billion annually treating childhood obesity, and $147 billion treating all forms of obesity.

Good stuff. We need to improve health in the USA. The current system is unhealthy and needs to be improved. The public good from improving the health of society is huge (both in terms of individual happiness and economic benefits).

Florence Nightingale: The passionate statistician

She brought about fundamental change in the British military medical system, preventing any such future calamities. To do it, she pioneered a brand-new method for bringing about social change: applied statistics.
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he statistics changed Nightingale’s understanding of the problems in Turkey. Lack of sanitation, she realized, had been the principal reason for most of the deaths, not inadequate food and supplies as she had previously thought.
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As impressive as her statistics were, Nightingale worried that Queen Victoria’s eyes would glaze over as she scanned the tables. So Nightingale devised clever ways of presenting the information in charts. Statistics had been presented using graphics only a few times previously, and perhaps never to persuade people of the need for social change.

Applied statistics is a tool available to all to achieve great improvement. Unfortunately it is still very underused. As George Box says: applied statistics is not about proving a theorem, it’s about being curious about things. The goal of design of experiments is to learn and refine your experiment based on the knowledge you gain and experiment again. It is a process of discovery.

Teenage Engineer’s Company Launches Safety Stair

Young engineer launches stair aid by Geoff Adams-Spink

A young woman from Sheffield has turned a GCSE coursework project into an award-winning stair-climbing device for older and disabled people. Ruth Amos has launched her StairSteady handrail at Naidex 2008 – the annual disability exhibition in Birmingham.

She told BBC News that she was inspired to create the device for the father of one of her teachers who had had a stroke. She won an award for her idea and has now set up a company to sell it. The StairSteady is a horizontal rail at 90 degrees to the wall or banister that people can hold on to as they go up or down stairs.
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The invention was then entered for the Young Engineer for Britain competition and won first prize.

Great stuff. Innovation doesn’t have to be amazing technology. Finding solutions that make people’s lives better is the key. And then showing some entrepreneurship is great, Ruth setup her company when she was 16. I wish her luck.

Engineering: Cellphone Microscope

UCLA Professor Aydogan Ozcan‘s invention (LUCAS) enables rapid counting and imaging of cells without using any lenses even within a working cell phone device. He placed cells directly on the imaging sensor of a cell phone. The imaging sensor captures a holographic image of the cells containing more information than a conventional microscope. The CelloPhone received a Wireless Innovations Award from Vodafone

a wireless health monitoring technology that runs on a regular cell-phone would significantly impact the global fight against infectious diseases in resource poor settings such as in Africa, parts of India, South-East Asia and South America.

The CelloPhone Project aims to develop a transformative solution to these global challenges by providing a revolutionary optical imaging platform that will be used to specifically analyze bodily fluids within a regular cell phone. Through wide-spread use of this innovative technology, the health care services in the developing countries will significantly be improved making a real impact in the life quality and life expectancy of millions.
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For most bio-medical imaging applications, directly seeing the structure of the object is of paramount importance. This conventional way of thinking has been the driving motivation for the last few decades to build better microscopes with more powerful lenses or other advanced imaging apparatus. However, for imaging and monitoring of discrete particles such as cells or bacteria, there is a much better way of imaging that relies on detection of their shadow signatures. Technically, the shadow of a micro-object can be thought as a hologram that is based on interference of diffracted beams interacting with each cell. Quite contrary to the dark shadows that we are used to seeing in the macro-world (such as our own shadow on the wall), micro-scale shadows (or transmission holograms) contain an extremely rich source of quantified information regarding the spatial features of the micro-object of interest.

By making use of this new way of thinking, unlike conventional lens based imaging approaches, LUCAS does not utilize any lenses, microscope-objectives or other bulk optical components, and it can immediately monitor an ultra-large field of view by detecting the holographic shadow of cells or bacteria of interest on a chip. The holographic diffraction pattern of each cell, when imaged under special conditions, is extremely rich in terms of spatial information related to the state of the cell or bacteria. Through advanced signal processing tools that are running at a central computer station, the unique texture of these cell/bacteria holograms will enable highly specific and accurate medical diagnostics to be performed even in resource poor settings by utilizing the existing wireless networks.

This is another great example of engineers creating technologically appropriate solutions.