Tiny Swimming Bio-Bots Boldly Go Where No Bot Has Swum Before

The alien world of aquatic micro-organisms just got new residents: synthetic self-propelled swimming bio-bots.

Engineers developed the first tiny, synthetic machines that can swim by themselves, powered by beating heart cells. (Credit: Alex Jerez Roman, Beckman Institute for Advanced Science and Technology)

A team of engineers has developed a class of tiny bio-hybrid machines that swim like sperm, the first synthetic structures that can traverse the viscous fluids of biological environments on their own. Led by Taher Saif, the University of Illinois Gutgsell Professor of mechanical science and engineering, the team published its work in the journal Nature Communications.
"Micro-organisms have a whole world that we only glimpse through the microscope," Saif said. "This is the first time that an engineered system has reached this underworld."
The bio-bots are modeled after single-celled creatures with long tails called flagella -- for example, sperm. The researchers begin by creating the body of the bio-bot from a flexible polymer. Then they culture heart cells near the junction of the head and the tail. The cells self-align and synchronize to beat together, sending a wave down the tail that propels the bio-bot forward.
This self-organization is a remarkable emergent phenomenon, Saif said, and how the cells communicate with each other on the flexible polymer tail is yet to be fully understood. But the cells must beat together, in the right direction, for the tail to move.
"It's the minimal amount of engineering -- just a head and a wire," Saif said. "Then the cells come in, interact with the structure, and make it functional."
See an animation of the bio-bots in motion and a video of a free-swimming bot.
The team also built two-tailed bots, which they found can swim even faster. Multiple tails also opens up the possibility of navigation. The researchers envision future bots that could sense chemicals or light and navigate toward a target for medical or environmental applications.
"The long-term vision is simple," said Saif, who is also part of the Beckman Institute for Advanced Science and Technology at the U. of I. "Could we make elementary structures and seed them with stem cells that would differentiate into smart structures to deliver drugs, perform minimally invasive surgery or target cancer?"
The swimming bio-bot project is part of a larger National Science Foundation-supported Science and Technology Center on Emergent Behaviors in Integrated Cellular Systems, which also produced the walking bio-bots developed at Illinois in 2012.
"The most intriguing aspect of this work is that it demonstrates the capability to use computational modeling in conjunction with biological design to optimize performance, or design entirely different types of swimming bio-bots," said center director Roger Kamm, a professor of biological and mechanical engineering at the Massachusetts Institute of Technology. "This opens the field up to a tremendous diversity of possibilities. Truly an exciting advance."

Journal Reference:

1. Brian J. Williams, Sandeep V. Anand, Jagannathan Rajagopalan, M. Taher A. Saif. A self-propelled biohybrid swimmer at low Reynolds number. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4081

Courtesy: ScienceDaily

Altering the Community of Gut Bacteria Promotes Health and Increases Lifespan

Scientists at the Buck Institute for Research on Aging have promoted health and increased lifespan in Drosophila by altering the symbiotic, or commensal, relationship between bacteria and the absorptive cells lining the intestine. The research, appearing in the January 16, 2014 edition of Cell, provides a model for studying many of the dysfunctions that are characteristic of the aging gut and gives credence to the growing supposition that having the right balance of gut bacteria may be key to enjoying a long healthy life.

Even though recent research in humans has linked the composition of gut flora with diet and health in the elderly and the list of age-related diseases associated with changes in gut bacteria include cancer, diabetes, and inflammatory bowel disease, lead author and Buck faculty Heinrich Jasper, PhD, says there is no systematic understanding of how we go from having a young, healthy gut to one that is old and decrepit. "Our study explores age-related changes in the gut that include increased oxidative stress, inflammation, impaired efficiency of the immune response, and the over-proliferation of stem cells," said Jasper. "It puts these changes into a hierarchical, causal relationship and highlights the points where we can intervene to rescue the negative results of microbial imbalance."
Jasper says the bacterial load in fly intestines increases dramatically with age, resulting in an inflammatory condition. The imbalance is driven by chronic activation of the stress response gene FOXO (something that happens with age), which suppresses the activity of a class of molecules (PGRP-SCs, homologues of PGLYRPs in humans) that regulate the immune response to bacteria. PGRP-SC suppression deregulates signaling molecules (Rel/NFkB) that are important to mount an effective immune response to gut bacteria. The resulting immune imbalance allows bacterial numbers to expand, triggering an inflammatory response that includes the production of free radicals. Free radicals, in turn, cause over-proliferation of stem cells in the gut, resulting in epithelial dysplasia, a pre-cancerous state.
Jasper said the most exciting result of their study occurred when his group increased the expression of PGRP-SC in epithelial cells of the gut, which restored the microbial balance and limited stem cell proliferation. This enhancement of PGRP-SC function, which could be mimicked by drugs, was sufficient to increase lifespan of flies. "If we can understand how aging affects our commensal population -- first in the fly and then in humans -- -- our data suggest that we should be able to impact health span and life span quite strongly, because it is the management of the commensal population that is critical to the health of the organism."
 

Journal Reference:

1. Linlin Guo, Jason Karpac, Susan L. Tran, Heinrich Jasper. PGRP-SC2 Promotes Gut Immune Homeostasis to Limit Commensal Dysbiosis and Extend Lifespan. Cell, 2014; 156 (1-2): 109 DOI: 10.1016/j.cell.2013.12.018

Courtesy: ScienceDaily
 

3-D Tissue Printing: Cells from the Eye Inkjet-Printed for the First Time

A group of researchers from the UK have used inkjet printing technology to successfully print cells taken from the eye for the very first time.

The breakthrough, which has been detailed in a paper published today, 18 December, in IOP Publishing's journal Biofabrication, could lead to the production of artificial tissue grafts made from the variety of cells found in the human retina and may aid in the search to cure blindness.
At the moment the results are preliminary and provide proof-of-principle that an inkjet printer can be used to print two types of cells from the retina of adult rats―ganglion cells and glial cells. This is the first time the technology has been used successfully to print mature central nervous system cells and the results showed that printed cells remained healthy and retained their ability to survive and grow in culture.
Co-authors of the study Professor Keith Martin and Dr Barbara Lorber, from the John van Geest Centre for Brain Repair, University of Cambridge, said: "The loss of nerve cells in the retina is a feature of many blinding eye diseases. The retina is an exquisitely organised structure where the precise arrangement of cells in relation to one another is critical for effective visual function."
"Our study has shown, for the first time, that cells derived from the mature central nervous system, the eye, can be printed using a piezoelectric inkjet printer. Although our results are preliminary and much more work is still required, the aim is to develop this technology for use in retinal repair in the future."
The ability to arrange cells into highly defined patterns and structures has recently elevated the use of 3D printing in the biomedical sciences to create cell-based structures for use in regenerative medicine.
In their study, the researchers used a piezoelectric inkjet printer device that ejected the cells through a sub-millimetre diameter nozzle when a specific electrical pulse was applied. They also used high speed video technology to record the printing process with high resolution and optimised their procedures accordingly.
"In order for a fluid to print well from an inkjet print head, its properties, such as viscosity and surface tension, need to conform to a fairly narrow range of values. Adding cells to the fluid complicates its properties significantly," commented Dr Wen-Kai Hsiao, another member of the team based at the Inkjet Research Centre in Cambridge.
Once printed, a number of tests were performed on each type of cell to see how many of the cells survived the process and how it affected their ability to survive and grow.
The cells derived from the retina of the rats were retinal ganglion cells, which transmit information from the eye to certain parts of the brain, and glial cells, which provide support and protection for neurons.
"We plan to extend this study to print other cells of the retina and to investigate if light-sensitive photoreceptors can be successfully printed using inkjet technology. In addition, we would like to further develop our printing process to be suitable for commercial, multi-nozzle print heads," Professor Martin concluded.

Journal Reference:

1. Barbara Lorber, Wen-Kai Hsiao, Ian M Hutchings, Keith R Martin. Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing. Biofabrication, 2014; 6 (1): 015001 DOI: 10.1088/1758-5082/6/1/015001

Novel Technology Reveals Aerodynamics of Migrating Birds Flying in a V-Formation

Researchers using custom-built GPS and accelerometer loggers, developed with funding from the Engineering and Physical Sciences Research Council, (EPSRC), and attached to free-flying birds on migration, have gained ground-breaking insights into the mysteries of bird flight formation.

 New research shows that birds precisely time when they flap their wings and position themselves in aerodynamic optimal positions, to maximize the capture of upwash, or 'good air', throughout the entire flap cycle, while avoiding areas of downwash or 'bad air'. (Credit: © brianguest / Fotolia)

he research, led by the Royal Veterinary College, University of London, proves for the first time that birds precisely time when they flap their wings and position themselves in aerodynamic optimal positions, to maximise the capture of upwash, or 'good air', throughout the entire flap cycle, while avoiding areas of downwash or 'bad air'.

It was previously not thought possible for birds to carry out such aerodynamic feats because of the complex flight dynamics and sensory feedback required. The study, is published in the journal Nature, on Thursday 16th January 2014.

Dr Steve Portugal, Lead Researcher at the Royal Veterinary College, University of London, said: "The distinctive V-formation of bird flocks has long intrigued researchers and continues to attract both scientific and popular attention, however a definitive account of the aerodynamic implications of these formations has remained elusive until now.

"The intricate mechanisms involved in V-formation flight indicate remarkable awareness and ability of birds to respond to the wingpath of nearby flock-mates. Birds in V-formation seem to have developed complex phasing strategies to cope with the dynamic wakes produced by flapping wings."

Professor David Delpy, Chief Executive of the EPSRC said: "This is a fascinating piece of research, providing a scientific answer to a question that I suspect most people have asked themselves -- why do birds fly in formation? The results will prove useful in a variety of fields for example aerodynamics and manufacturing.

"The research is an excellent example of an international collaboration involving inputs not only from many physical and engineering science disciplines, but also the life sciences."

The mechanisms that the birds use is achieved firstly through spatial phasing of wing beats when flying in a spanwise ('V') position, creating wing-tip path coherence between individuals which will maximise upwash capture throughout the entire flap cycle.

Secondly, when flying in a streamwise ('behind') position, birds exhibit spatial anti-phasing of their wing beats, creating no wing-tip path coherence and avoiding regions of detrimental downwash. Such a mechanism would be available specifically to flapping formation flight.

Scientists captured the data for the study as the birds flew alongside a micro-light on their migration route from their summer birthplace in Austria to their wintering grounds in Tuscany, Italy. The study is the first to collect data from free-flying birds and was made possible by the logging devices custom-built at the Structure and Motion Laboratory at the Royal Veterinary College.

The light-weight, synchronised, GPS and inertial measurement devices, recorded within up to 30 cm accuracy where a bird was within the flock, its speed, and when and how hard it flapped its wings. The precision of the measurements enabled the aerodynamic interactions of the birds to be studied at a level and complexity for the first time.

Dr Portugal and his team worked with the Waldrappteam, a conservation organisation based in Austria, who are re-introducing Northern Bald Ibises into Europe, after being extinct there for 300 years.

The 14 juvenile birds used in the study were hand-reared at Vienna Zoo by human foster parents from the Waldrappteam. The birds were trained to follow a micro-light 'mother-ship' to teach them their historic migration routes to wintering grounds in Italy. Normally they would learn this from adult birds, and without this help, the birds would not thrive.

The birds are currently in Tuscany and the team hopes they will remember the way to what should be their breeding grounds in Salzburg later this year, without the help of the micro-light this time!

Journal Reference:

1. Steven J. Portugal, Tatjana Y. Hubel, Johannes Fritz, Stefanie Heese, Daniela Trobe, Bernhard Voelkl, Stephen Hailes, Alan M. Wilson, James R. Usherwood. Upwash exploitation and downwash avoidance by flap phasing in ibis formation flight. Nature, 2014; 505 (7483): 399 DOI: 10.1038/nature12939

Courtesy: ScienceDaily

 

Research Demonstrates 'Guided Missile' Strategy to Kill Hidden HIV

Researchers at the UNC School of Medicine have deployed a potential new weapon against HIV -- a combination therapy that targets HIV-infected cells that standard therapies cannot kill.

Scanning electron micrograph of HIV-1 virions budding from a cultured lymphocyte. (Credit: CDC/C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus)

Using mouse models that have immune systems composed of human cells, researchers led by J. Victor Garcia, PhD, found that an antibody combined with a bacterial toxin can penetrate HIV-infected cells and kill them even though standard antiretroviral therapy, also known as ART, had no effect. Killing these persistent, HIV-infected cells is a major impediment to curing patients of HIV.
"Our work provides evidence that HIV-infected cells can be tracked down and destroyed throughout the body," said Garcia, professor of medicine and senior author of the study published January 9 in the journal PloS Pathogens.
For people with HIV, ART is life-saving treatment that can reduce the amount of virus in the body to undetectable levels. But as soon as treatment is stopped, the virus begins to replicate again. This means that people with HIV must be on medications for life. For some people, therapies are not without serious side effects.
In patients on ART, the virus either remains dormant or it multiplies very slowly -- it persists, hidden, even though a cocktail of drugs is aligned against it.
Garcia's findings advance the so-called "kick-and-kill" strategy for HIV eradication -- if the persistent virus is exposed, it can be targeted and killed with a new therapy.
To attack persistent HIV-infected cells, Garcia and colleagues used humanized bone marrow/liver/thymus mice -- or BLT mice -- with entire immune systems composed of human cells. This allows his team to study the distribution of persistent HIV-infected cells throughout the body and test strategies to eliminate those cells.
For the PloS Pathogens study, the researchers first treated the mice with an ART cocktail of three different drugs. Despite using strong concentrations of all three drugs, the researchers found that the virus managed to survive in immune cells in all tissues they analyzed, including the bone marrow, spleen, liver, lung, and gut.
Then they used a compound developed by co-authors Edward Berger, PhD, and Ira Pastan, PhD, from the National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health). The compound is an antibody called 3B3 combined with a bacterial toxin called PE38. The researchers hypothesized that the antibody would first recognize cells expressing a specific HIV protein on the surface of infected cells. The antibody would attach to the protein and allow the toxin to enter and kill the infected cells.
When Garcia's team treated humanized HIV-infected and ART-treated mice with the 3B3-PE38 compound and then looked for infected cells in tissues, they found that the molecular missile had killed the vast majority of persistent HIV-infected cells that had been actively producing the virus despite traditional therapy, resulting in a six-fold drop in the number of infected cells throughout the immune systems.
While this reduction fell short of complete eradication, the finding offers a new route of investigation as part of the multi-pronged "kick-and-kill" strategy.
"The BLT model represents a platform in which virtually any novel approach to HIV eradication can be tested," Garcia said. "It helps us prioritize which therapeutic approaches should be advanced to clinical implementation in humans. This study shows that it's possible to attack and kill hidden HIV-infected cells that standard therapy can't touch."
 

Journal Reference:

1. Paul W. Denton, Julie M. Long, Stephen W. Wietgrefe, Craig Sykes, Rae Ann Spagnuolo, Olivia D. Snyder, Katherine Perkey, Nancie M. Archin, Shailesh K. Choudhary, Kuo Yang, Michael G. Hudgens, Ira Pastan, Ashley T. Haase, Angela D. Kashuba, Edward A. Berger, David M. Margolis, J. Victor Garcia. Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART. PLoS Pathogens, 2014; 10 (1): e1003872 DOI: 10.1371/journal.ppat.1003872

Courtesy: ScienceDaily

Researchers Develop Artificial Bone Marrow; May Be Used to Reproduce Hematopoietic Stem Cells

Artificial bone marrow may be used to reproduce hematopoietic stem cells. A prototype has now been developed by scientists of KIT, the Max Planck Institute for Intelligent Systems, Stuttgart, and Tübingen University. The porous structure possesses essential properties of natural bone marrow and can be used for the reproduction of stem cells at the laboratory. This might facilitate the treatment of leukemia in a few years.

Scanning electron microscopy of stem cells (yellow / green) in a scaffold structure (blue) serving as a basis for the artificial bone marrow. (Credit: C. Lee-Thedieck/KIT)

The researchers are now presenting their work in the journal Biomaterials.
Blood cells, such as erythrocytes or immune cells, are continuously replaced by new ones supplied by hematopoietic stem cells located in a specialized niche of the bone marrow. Hematopoietic stem cells can be used for the treatment of blood diseases, such as leukemia. The affected cells of the patient are replaced by healthy hematopoietic stem cells of an eligible donor.
However, not every leukemia patient can be treated in this way, as the number of appropriate transplants is not sufficient. This problem might be solved by the reproduction of hematopoietic stem cells. So far, this has been impossible, as these cells retain their stem cell properties in their natural environment only, i.e. in their niche of the bone marrow. Outside of this niche, the properties are modified. Stem cell reproduction therefore requires an environment similar to the stem cell niche in the bone marrow.
The stem cell niche is a complex microscopic environment having specific properties. The relevant areas in the bone are highly porous and similar to a sponge. This three-dimensional environment does not only accommodate bone cells and hematopoietic stem cells but also various other cell types with which signal substances are exchanged. Moreover, the space among the cells has a matrix that ensures a certain stability and provides the cells with points to anchor. In the stem cell niche, the cells are also supplied with nutrients and oxygen.
The Young Investigators Group "Stem Cell-Material Interactions" headed by Dr. Cornelia Lee-Thedieck consists of scientists of the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart, and Tübingen University. It artificially reproduced major properties of natural bone marrow at the laboratory. With the help of synthetic polymers, the scientists created a porous structure simulating the sponge-like structure of the bone in the area of the blood-forming bone marrow. In addition, they added protein building blocks similar to those existing in the matrix of the bone marrow for the cells to anchor. The scientists also inserted other cell types from the stem cell niche into the structure in order to ensure substance exchange.
Then, the researchers introduced hematopoietic stem cells isolated from cord blood into this artificial bone marrow. Subsequent breeding of the cells took several days. Analyses with various methods revealed that the cells really reproduce in the newly developed artificial bone marrow. Compared to standard cell cultivation methods, more stem cells retain their specific properties in the artificial bone marrow.
The newly developed artificial bone marrow that possesses major properties of natural bone marrow can now be used by the scientists to study the interactions between materials and stem cells in detail at the laboratory. This will help to find out how the behavior of stem cells can be influenced and controlled by synthetic materials. This knowledge might contribute to producing an artificial stem cell niche for the specific reproduction of stem cells and the treatment of leukemia in ten to fifteen years from now.
 

Journal Reference:

1. Annamarija Raic, Lisa Rödling, Hubert Kalbacher, Cornelia Lee-Thedieck. Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells. Biomaterials, 2014; 35 (3): 929 DOI: 10.1016/j.biomaterials.2013.10.038

Courtesy: ScienceDaily
 

Evidence of Harmful Effect of Bisphenol A-Based Plastics

Bisphenol A impairs the function of proteins that are vital for growth processes in cells. This finding has been reported by researchers from the Ruhr-Universität Bochum and the University of Wuppertal. The substance, short BPA, is contained in many plastic products and is suspected of being hazardous to health. To date, it had been assumed that bisphenol A produces a harmful effect by binding to hormone receptors. The chemist and biochemist team has discovered that the substance also affects the so-called small GTPases. They published their findings in the Journal of Medicinal Chemistry.

 

Bisphenol A binds to the switch protein K-Ras, which is vital for cell growth processes and plays a role in tumourigenesis. (Credit: RUB, Diagram: Miriam Schöpel)

 Complex mechanism of action

"Our research provides further evidence that the physiological effects of bisphenol A may be even more complex than previously assumed," says Prof Dr Raphael Stoll, head of Biomolecular Spectroscopy at the Ruhr-Universität. "However, we have also discovered other related compounds that indicate which path the future development of pharmaceutically effective substances against GTPase-mediated tumours may take," adds synthetic chemist Prof Dr Jürgen Scherkenbeck from Wuppertal.
Bisphenol A impairs the function of GTPases
Small GTPases are enzymes that occur in two states within the cell: in the active form when bound to the GTP molecule; and in the inactive form when bound to GDP, a lower-energy form of GTP. These switch proteins are crucial for transmitting signals within the cell. The researchers have demonstrated that bisphenol A binds to two different small GTPases, K-Ras and H-Ras, thereby preventing the exchange of GDP for GTP. The non-profit organisation German Cancer Aid (Deutsche Krebshilfe e. V.) has financed the project since 2011.
Bisphenol A is a suspected health hazard
Various organisations have pointed out that bisphenol A may be hazardous to health: the Federal Institute for Risk Assessment (Bundesinstitut für Risikoforschung), the European Food Safety Authority, the US Food and Drug Administration (FDA), the US National Institutes of Health (NIH) and the US-American Breast Cancer Foundation. However, those organisations have not yet provided a final assessment of the substance's hazardous potential. Nevertheless, the European Commission banned the use of bisphenol A in the manufacture of baby bottles in 2011. Academic studies indicate that the substance may increase the risk of cardiovascular diseases, breast and prostate cancer as well as neuronal diseases. The researchers therefore recommend a restriction of bisphenol A-based plastic containers for food products.
 

Journal Reference:

1. Miriam Schöpel, Katharina F. G. Jockers, Peter M. Düppe, Jasmin Autzen, Veena N. Potheraveedu, Semra Ince, King Tuo Yip, Rolf Heumann, Christian Herrmann, Jürgen Scherkenbeck, Raphael Stoll. Bisphenol A Binds to Ras Proteins and Competes with Guanine Nucleotide Exchange: Implications for GTPase-Selective Antagonists. Journal of Medicinal Chemistry, 2013; 56 (23): 9664 DOI: 10.1021/jm401291q

Courtesy: ScienceDaily