Tag: Biotechnology (Ethics)

Categories
News

* Nottingham Dollies prove cloned sheep can live long and healthy lives

Three weeks after the scientific world marked the 20th anniversary of the birth of Dolly the sheep new research, published by The University of Nottingham, in the academic journal Nature Communications has shown that four clones derived from the same cell line — genomic copies of Dolly — reached their 8th birthdays in good health.

Nottingham’s Dollies — Debbie, Denise, Dianna and Daisy — have just celebrated their 9th birthdays and along with nine other clones they are part of a unique flock of cloned sheep under the care of Professor Kevin Sinclair, an expert in developmental biology, in the School of Biosciences.

The research — ‘Healthy ageing of cloned sheep’ — is the first detailed and comprehensive assessment of age-related non-communicable disease in cloned offspring. Published today, Tuesday 26 July 2016, it shows that at between seven to nine years of age (60 to 70 in human years) these cloned sheep were showing no long-term detrimental health effects.

Dolly made history as the first animal to be cloned from an adult cell using a technique known as somatic-cell nuclear transfer (SCNT). The late, Professor Keith Campbell was instrumental in this pioneering work. In 1999 he joined The University of Nottingham where he continued his research in reproductive biology until his death in 2012. The flock of clones are his legacy to the University.

This latest study was led by Professor Kevin Sinclair, a close colleague of Professor Campbell’s.

Professor Sinclair said: “Despite technological advances in recent years’ efficiency of SCNT remains low but there are several groups across the world working on this problem at present and there is reason to be optimistic that there will be significant improvements in future. These improvements will stem from a better understanding of the underlying biology related to the earliest stages of mammalian development. In turn this could lead to the realistic prospect of using SCNT to generate stem cells for therapeutic purposes in humans as well as generating transgenic animals that are healthy, fertile and productive. However, if these biotechnologies are going to be used in future we need to continue to test their safety.”

Nottingham’s oldest clone was born in July 2006. The four Finn-Dorset clones — ‘the Dollies’ — were born in July 2007. A female Lleyn clone was born in August 2007 along with a second clone (breed unknown). In June 2008 six more Lleyn ewes were born.

These animals originated from studies undertaken by Professor Campbell between 2005 and 2007 which sought to improve the efficiency of SCNT. The four Finn Dorsets were derived from the mammary gland cell line that led to the birth of Dolly. The other clones came from fetal fibroblasts.

Longevity and healthy ageing among SCNT clones have long been contentious issues and much was made of Dolly having to undergo treatment for osteoarthritis some time prior to her death in 2003 at six years old.

During 2015 Nottingham’s cloned sheep underwent a series of comprehensive assessments for non-communicable diseases including obesity, hypertension and osteoarthritis — three major comorbidities in aged human populations. The examinations included the use of anaesthesia to carry out x-rays and MRI scans.

The research was carried out under the authority of the United Kingdom Animal (Scientific Procedures) Act 1986 with approval from The University of Nottingham Animal Welfare and Ethical Review Board.

The flock was tested for glucose tolerance and insulin sensitivity. They underwent radio-telemetric assessments to check their heart rate and blood pressure. They had a full musculoskeletal examination carried out by Dr Sandra Corr, a veterinary orthopaedic specialist from the University’s School of Veterinary Medicine and Science and a co-author of this research.

Radiological examinations of all main joints were followed by MRI scans of their knees, the joint most affected by osteoarthritis in Dolly. Their health was compared with a group of naturally bred six-year-old sheep living under similar conditions at the University.

Professor Sinclair said: “Healthy ageing of SCNT clones has never been properly investigated. There have been no detailed studies of their health. One of the concerns in the early days was that cloned offspring were ageing prematurely and Dolly was diagnosed with osteoarthritis at the age of around five, so clearly this was a relevant area to investigate. Following our detailed assessments of glucose tolerance, insulin sensitivity, blood pressure and musculoskeletal investigations we found that our clones, considering their age, were at the time of our research healthy.”

Despite their advanced age the cloned sheep — including the four Dollies — were showing no signs of diabetes, high blood pressure, or clinical degenerative-joint disease. Although some of the animals were showing radiographic evidence of mild, and in Debbie’s case, moderate osteoarthritis none of the animals were lame and none required treatment for osteoarthritis.

There is still a long way to go before SCNT is perfected. However, this research has shown that cloned animals can live long and healthy lives.

Professor Sinclair said: “It is well established that prior to conception and in the early stages of pregnancy during natural or assisted reproduction subtle chemical changes can affect the human genome leading to development and late-onset chronic diseases. Given that SCNT requires the use of assisted reproductive procedures it is important to establish if similar diseases or disorders exist in apparently healthy aged cloned offspring.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160726122958.htm Original web page at Science

Categories
News

Scientists grow mini human brains

Scientists in Singapore have made a big leap on research on the ‘mini-brain’. These advanced mini versions of the human midbrain will help researchers develop treatments and conduct other studies into Parkinson’s Disease (PD) and aging-related brain diseases.

These mini midbrain versions are three-dimensional miniature tissues that are grown in the laboratory and they have certain properties of specific parts of the human brains. This is the first time that the black pigment neuromelanin has been detected in an organoid model. The study also revealed functionally active dopaminergic neurons.

The human midbrain, which is the information superhighway, controls auditory, eye movements, vision and body movements. It contains special dopaminergic neurons that produce dopamine — which carries out significant roles in executive functions, motor control, motivation, reinforcement, and reward. High levels of dopamine elevate motor activity and impulsive behaviour, whereas low levels of dopamine lead to slowed reactions and disorders like PD, which is characterised by stiffness and difficulties in initiating movements.

Also causing PD is the dramatic reduction in neuromelanin production, leading to the degenerative condition of patients, which includes tremors and impaired motor skills. This creation is a key breakthrough for studies in PD, which affects an estimated seven to 10 million people worldwide. Furthermore, there are people who are affected by other causes of parkinsonism. Researchers now have access to the material that is affected in the disease itself, and different types of studies can be conducted in the laboratory instead of through simulations or on animals. Using stem cells, scientists have grown pieces of tissue, known as brain organoids, measuring about 2 to 3 mm long. These organoids contain the necessary hallmarks of the human midbrain, which are dopaminergic neurons and neuromelanin.

Jointly led by Prof Ng Huck Hui from A*STAR’s Genome Institute of Singapore (GIS) and Assistant Prof Shawn Je from Duke-NUS Medical School, this collaborative research between GIS, Duke-NUS, and the National Neuroscience Institute (NNI) is funded by the National Medical Research Council’s Translational Clinical Research (TCR) Programme In Parkinson’s disease (PD) and A*STAR. Other collaborators are from the Lieber Institute for Brain Development, the Johns Hopkins University School of Medicine, and the Nanyang Technological University.

Assistant Prof Shawn Je from Duke-NUS Medical School’s Neuroscience & Behavioural Disorders Programme said, “It is remarkable that our midbrain organoids mimic human midbrain development. The cells divide, cluster together in layers, and become electrically and chemically active in three-dimensional environment like our brain. Now we can really test how these mini brains react to existing or newly developed drugs before treating patients, which will be a game changer for drug development.”

Prof Tan Eng King, Research Director and Senior Consultant, Department of Neurology at NNI and Lead PI of the TCR Programme in PD, remarked, “The human brain is arguably the most complex organ and chronic brain diseases pose considerable challenges to doctors and patients. This achievement by our Singapore team represents an initial but momentous scientific landmark as we continue to strive for better therapies for our patients.”

GIS Executive Director Prof Ng Huck Hui said, “Considering one of the biggest challenges we face in PD research is the lack of accessibility to the human brains, we have achieved a significant step forward. The midbrain organoids display great potential in replacing animals’ brains which are currently used in research; we can now use these midbrains in culture instead to advance our understanding and future studies for the disease, and perhaps even other related diseases.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160730154504.htm Original web page at Science Daily

Categories
News

Artificial pancreas likely to be available by 2018

 

The artificial pancreas — a device which monitors blood glucose in patients with type 1 diabetes and then automatically adjusts levels of insulin entering the body — is likely to be available by 2018, conclude authors of a paper in Diabetologia (the journal of the European Association for the Study of Diabetes). Issues such as speed of action of the forms of insulin used, reliability, convenience and accuracy of glucose monitors plus cybersecurity to protect devices from hacking, are among the issues that are being addressed.

Currently available technology allows insulin pumps to deliver insulin to people with diabetes after taking a reading or readings from glucose meters, but these two components are separate. It is the joining together of both parts into a ‘closed loop’ that makes an artificial pancreas, explain authors Dr Roman Hovorka and Dr Hood Thabit of the University of Cambridge, UK. “In trials to date, users have been positive about how use of an artificial pancreas gives them ‘time off’ or a ‘holiday’ from their diabetes management, since the system is managing their blood sugar effectively without the need for constant monitoring by the user,” they say.

One part of the clinical need for the artificial pancreas is the variability of insulin requirements between and within individuals — on one day a person could use one third of their normal requirements, and on another 3 times what they normally would. This is dependent on the individual, their diet, their physical activity and other factors. The combination of all these factors together places a burden on people with type 1 diabetes to constantly monitor their glucose levels, to ensure they don’t end up with too much blood sugar (hyperglycaemic) or more commonly, too little (hypoglycaemic). Both of these complications can cause significant damage to blood vessels and nerve endings, making complications such as cardiovascular problems more likely.

There are alternatives to the artificial pancreas, with improvements in technology in both whole pancreas transplantation and also transplants of just the beta cells from the pancreas which produce insulin. However, recipients of these transplants require drugs to supress their immune systems just as in other organ transplants. In the case of whole pancreas transplantation, major surgery is required; and in beta cell islet transplantation, the body’s immune system can still attack the transplanted cells and kill off a large proportion of them (80% in some cases). The artificial pancreas of course avoids the need for major surgery and immunosuppressant drugs.

Researchers globally continue to work on a number of challenges faced by artificial pancreas technology. One such challenge is that even fast-acting insulin analogues do not reach their peak levels in the bloodstream until 0.5 to 2 hours after injection, with their effects lasting 3 to 5 hours. So this may not be fast enough for effective control in, for example, conditions of vigorous exercise. Use of the even faster acting ‘insulin aspart’ analogue may remove part of this problem, as could use of other forms of insulin such as inhaled insulin. Work also continues to improve the software in closed loop systems to make it as accurate as possible in blood sugar management.

A number of clinical studies have been completed using the artificial pancreas in its various forms, in various settings such as diabetes camps for children, and real life home testing. Many of these trials have shown as good or better glucose control than existing technologies (with success defined by time spent in a target range of ideal blood glucose concentrations and reduced risk of hypoglycaemia). A number of other studies are ongoing. The authors say: “Prolonged 6- to 24-month multinational closed-loop clinical trials and pivotal studies are underway or in preparation including adults and children. As closed loop devices may be vulnerable to cybersecurity threats such as interference with wireless protocols and unauthorised data retrieval, implementation of secure communications protocols is a must.”

The actual timeline to availability of the artificial pancreas, as with other medical devices, encompasses regulatory approvals with reassuring attitudes of regulatory agencies such as the US Food and Drug Administration (FDA), which is currently reviewing one proposed artificial pancreas with approval possibly as soon as 2017. And a recent review by the UK National Institute of Health Research (NIHR) reported that automated closed-loop systems may be expected to appear in the (European) market by the end of 2018. The authors say: “This timeline will largely be dependent upon regulatory approvals and ensuring that infrastructures and support are in place for healthcare professionals providing clinical care. Structured education will need to continue to augment efficacy and safety.”

The authors say: “Cost-effectiveness of closed-loop is to be determined to support access and reimbursement. In addition to conventional endpoints such as blood sugar control, quality of life is to be included to assess burden of disease management and hypoglycaemia. Future research may include finding out which sub-populations may benefit most from using an artificial pancreas. Research is underway to evaluate these closed-loop systems in the very young, in pregnant women with type 1 diabetes, and in hospital in-patients who are suffering episodes of hyperglycaemia.”

They conclude: “Significant milestones moving the artificial pancreas from laboratory to free-living unsupervised home settings have been achieved in the past decade. Through inter-disciplinary collaboration, teams worldwide have accelerated progress and real-world closed-loop applications have been demonstrated. Given the challenges of beta-cell transplantation, closed-loop technologies are, with continuing innovation potential, destined to provide a viable alternative for existing insulin pump therapy and multiple daily insulin injections.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160630214503.htm  Original web page at Science Daily

Categories
News

Electronic nose smells pesticides, nerve gas

The best-known electronic nose is the breathalyser. As drivers breathe into the device, a chemical sensor measures the amount of alcohol in their breath. This chemical reaction is then converted into an electronic signal, allowing the police officer to read off the result. Alcohol is easy to detect, because the chemical reaction is specific and the concentration of the measured gas is fairly high. But many other gases are complex mixtures of molecules in very low concentrations. Building electronic noses to detect them is thus quite a challenge.

Researchers from KU Leuven have now built a very sensitive electronic nose with metal-organic frameworks (MOFs). “MOFs are like microscopic sponges,” postdoctoral researcher Ivo Stassen explains. “They can absorb quite a lot of gas into their minuscule pores.”

“We created a MOF that absorbs the phosphonates found in pesticides and nerve gases. This means you can use it to find traces of chemical weapons such as sarin or to identify the residue of pesticides on food. This MOF is the most sensitive gas sensor to date for these dangerous substances. Our measurements were conducted in cooperation with imec, the Leuven-based nanotechnology research centre. The concentrations we’re dealing with are extremely low: parts per billion — a drop of water in an Olympic swimming pool — and parts per trillion.”

The chemical sensor can easily be integrated into existing electronic devices, Professor Rob Ameloot adds. “You can apply the MOF as a thin film over the surface of, for instance, an electric circuit. Therefore, it’s fairly easy to equip a smartphone with a gas sensor for pesticides and nerve gas.”

“Further research will allow us to examine other applications as well,” Professor Ameloot continues. “MOFs can measure very low concentrations, so we could use them to screen someone’s breath for diseases such as lung cancer and MS in an early stage. Or we could use the signature scent of a product to find out whether food has gone bad or to distinguish imitation wine from the original. This technology, in other words, offers a wide range of perspectives.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160704082706.htm Original web page at Science Daily 

Categories
News

Cats seem to grasp the laws of physics

Cats understand the principle of cause and effect as well as some elements of physics. Combining these abilities with their keen sense of hearing, they can predict where possible prey hides. These are the findings of researchers from Kyoto University in Japan, led by Saho Takagi and published in Springer’s journal Animal Cognition.

Previous work conducted by the Japanese team established that cats predict the presence of invisible objects based on what they hear. In the present study, the researchers wanted to find out if cats use a causal rule to infer if a container holds an object, based on whether it is shaken along with a sound or not. The team also wanted to establish if cats expect an object to fall out or not, once the container is turned over.

Thirty domestic cats were videotaped while an experimenter shook a container. In some cases this action went along with a rattling sound. In others it did not, to simulate that the vessel was empty. After the shaking phase, the container was turned over, either with an object dropping down or not.

Two experimental conditions were congruent with physical laws, where shaking was accompanied by a (no) sound and an (no) object to fall out of the container. The other two conditions were incongruent to the laws of physics. Either a rattling sound was followed by no object dropping out of the container or no sound while shaking led to a falling object.

The cats looked longer at the containers which were shaken together with a noise. This suggests that cats used a physical law to infer the existence (or absence) of objects based on whether they heard a rattle (or not). This helped them predict whether an object would appear (or not) once the container was overturned.

The animals also stared longer at containers in incongruent conditions, meaning an object dropped despite its having been shaken noiselessly or the other way around. It is as if the cats realized that such conditions did not fit into their grasp of causal logic.

“Cats use a causal-logical understanding of noise or sounds to predict the appearance of invisible objects,” says Takagi.

Researchers suggest that species’ surroundings influence their ability to find out information based on what they hear. The ecology of cats’ natural hunting style may therefore also favor the ability for inference on the basis of sounds. Takagi explains that hunting cats often need to infer the location or the distance of their prey from sounds alone because they stake out places of poor visibility. Further research is needed to find out exactly what cats see in their mind’s eye when they pick up noises, and if they can extract information such as quantity and size from what they hear.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/06/160614114410.htm  Original web page at Science Daily

Categories
News

Artificial synapse rivals biological ones in energy consumption

Creation of an artificial intelligence system that fully emulates the functions of a human brain has long been a dream of scientists. A brain has many superior functions as compared with super computers, even though it has light weight, small volume, and consumes extremely low energy. This is required to construct an artificial neural network, in which a huge amount (1014) of synapses is needed.

Most recently, great efforts have been made to realize synaptic functions in single electronic devices, such as using resistive random access memory (RRAM), phase change memory (PCM), conductive bridges, and synaptic transistors. Artificial synapses based on highly aligned nanostructures are still desired for the construction of a highly-integrated artificial neural network.

Prof. Tae-Woo Lee, research professor Wentao Xu, and Dr. Sung-Yong Min with the Dept. of Materials Science and Engineering at POSTECH have succeeded in fabricating an organic nanofiber (ONF) electronic device that emulates not only the important working principles and energy consumption of biological synapses but also the morphology. They recently published their findings in Science Advances, a new sister journal of Science.

The morphology of ONFs is very similar to that of nerve fibers, which form crisscrossing grids to enable the high memory density of a human brain. Especially, based on the e-Nanowire printing technique, highly-aligned ONFs can be massively produced with precise control over alignment and dimension. This morphology potentially enables the future construction of high-density memory of a neuromorphic system.

Important working principles of a biological synapse have been emulated, such as paired-pulse facilitation (PPF), short-term plasticity (STP), long-term plasticity (LTP), spike-timing dependent plasticity (STDP), and spike-rate dependent plasticity (SRDP). Most amazingly, energy consumption of the device can be reduced to a femtojoule level per synaptic event, which is a value magnitudes lower than previous reports. It rivals that of a biological synapse. In addition, the organic artificial synapse devices not only provide a new research direction in neuromorphic electronics but even open a new era of organic electronics.

This technology will lead to the leap of brain-inspired electronics in both memory density and energy consumption aspects. The artificial synapse developed by Prof. Lee’s research team will provide important potential applications to neuromorphic computing systems and artificial intelligence systems for autonomous cars (or self-driving cars), analysis of big data, cognitive systems, robot control, medical diagnosis, stock trading analysis, remote sensing, and other smart human-interactive systems and machines in the future.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160620100319.htm  Original web page at Science Daily

Categories
News

US government issues historic $3.5-million fine over animal welfare

Antibody provider Santa Cruz Biotechnology settles with government after complaints about treatment of goats. Santa Cruz Biotech has used goats to produce antibodies.

The US government has fined Santa Cruz Biotechnology, a major antibody provider, US$3.5 million over alleged violations of the US Animal Welfare Act. The penalty from the US Department of Agriculture is the largest in the agency’s history.

The company, which is headquartered in Dallas, Texas, will pay the fine as part of a settlement with the US Department of Agriculture (USDA). The agency had lodged three animal-welfare complaints against Santa Cruz Biotech, after USDA inspectors found evidence that the company mistreated goats at its facility in California.

Santa Cruz Biotech contested the government complaints, and the 19 May settlement agreement says that the company “neither admits nor denies” that it violated US animal-welfare regulations.

The settlement also permanently revokes Santa Cruz Biotech’s government licence to sell, buy, trade or import animals. And it requires the company to cancel its registration to operate as a research facility that uses animals. The company had extracted antibodies for research from animals such as goats and rabbits after injecting the animals with proteins to stimulate antibody production.

Neither Santa Cruz Biotech nor representatives of Covington & Burling, a Washington DC law firm that represents the company, have responded to Nature’s request for comment on the settlement.

Cathy Liss, president of the Animal Welfare Institute, an advocacy group in Washington DC, says that she is shocked by the unprecedented size of the fine on Santa Cruz Biotech. The largest previous fine that the USDA had imposed for animal-welfare complaints was a $270,000 penalty levied in 2011 against Feld Entertainment, which operates the Ringling Brothers and Barnum & Bailey Circus.

The settlement with Santa Cruz Biotech marks the end of a long-running investigation of the company’s animal-welfare practices. The USDA has lodged three animal-welfare complaints against Santa Cruz Biotech since 2007, after agency inspectors reported finding problems such as goats with untreated coyote bites and massive tumours, and rabbits being housed in cruel conditions. USDA inspectors also discovered that Santa Cruz was keeping 841 goats in a hidden facility.

In February, Nature reported that more than 5,000 goats and rabbits had disappeared from Santa Cruz’s facilities before a scheduled hearing on the USDA complaints. Santa Cruz would not confirm whether the animals were killed or sold.

After news of the animals’ disappearance became public, some scientists took to social media to call for a boycott of Santa Cruz’s products. Among them was Stephen Floor, a biologist at the University of California, Berkeley, who says that his lab has since sought out other antibody providers.

Floor says that losing Santa Cruz as an antibody provider will create extra work for researchers. Because the quality and type of antibodies varies widely, individual labs often stick with products from a single company to ensure that their experiments are replicable. “That said, I think any scientist will happily do that work in order to ensure that animal rights are a priority,” he says.

Nature doi:10.1038/nature.2016.19958

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/us-government-issues-historic-3-5-million-fine-over-animal-welfare-1.19958  Original web page at Nature

Categories
News

Targeting metals to fight pathogenic bacteria

Researchers at the Laboratory for Molecular Infection Medicine Sweden (MIMS) at Umeå University in Sweden participated in the discovery of a unique system of acquisition of essential metals in the pathogenic bacterium Staphylococcus aureus. This research was led by scientists at the CEA in France, in collaboration with researchers at the University of Pau, the INRA and the CNRS. It represents a new potential target for the design of antibiotics. These results are being published in the journal Science on Friday 27 May.

Metals are necessary for life and pathogenic bacteria have developed elaborate systems to compensate for the low concentration of these essential metals in their environment, in particular within a host. The case of iron is particularly well documented with, in some bacteria, the production of molecules called siderophores that specifically capture iron in the medium. Researchers have now identified a new metal scavenging molecule produced in the bacterium Staphylococcus aureus and baptized it staphylopine.

The researchers highlighted the role of the key players that allow the pathogen to acquire a wide range of essential metals in the environment, such as nickel, zinc, cobalt, copper and iron. Three enzymes, whose functions were unknown so far, allow the production of staphylopine by the combination of three building blocks (D-histidine, amino butyrate and pyruvate). An export system expels staphylopine out of the cell where it traps the target metals from the extracellular medium. The staphylopine / metal duo can then be picked up by the cell via a specific import system. In the absence of these import / export systems, the virulence of Staphylococcus aureus was known to be reduced, although the origins of this phenomenon were not fully understood.

“Remarkably, a few years ago we found that many, taxonomically unrelated, bacteria can release high concentrations of a wide variety of D-amino acids to the environment. Therefore, D-histidine might be just one D-amino acid of many that could serve as a building block for novel staphylopine-like molecules,” explained Felipe Cava from MIMS/Umeå University.

The discovery of staphylopine, how it is built, and how it is transported by these systems could now lead the way for the development of a new strategy against pathogenic bacteria, by targeting their addiction to metals.

Surprisingly, staphylopine closely resembles nicotianamine, a molecule that is found in all plants and that ensures the transport of essential metals from the roots, where they are collected, to the various aerial organs. The discovery of a similar metal scavenger in the three kingdoms of life (archaea, eukaryotes and now bacteria) suggests an ancient origin for this type of molecule.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160526151937.htm Original web page at Science Daily

Categories
News

Individualized cancer treatment targeting the tumor, not the whole body, a step closer

They look like small, translucent gems but these tiny ‘gel’ slivers hold the world of a patient’s tumour in microcosm ready for trials of anti-cancer drugs to find the best match between treatment and tumour.

The ‘gel’ is a new 3D printable material developed by QUT researchers that opens the way to rapid, personalised cancer treatment by enabling multiple, simultaneous tests to find the correct therapy to target a particular tumour.

Professor Dietmar W. Hutmacher from QUT’s Institute of Health and Biomedical Innovation said the new material was a gelatine-based hydrogel that mimicked human tissue. The method for producing the gelatine-based hydrogel is published in the journal Nature Protocols.

“Hydrogel is a biomaterial used by thousands of researchers around the globe; gelatine is based on collagen, one of the most common tissues in the human body. We have modified the gelatine to engineer 3D tumour microenvironments,” Professor Hutmacher said.

“Our big breakthrough is we can produce this high-quality material on a very large scale inexpensively.

“It is highly reproducible which means we have been able to produce this hydrogel hundreds of times, not just once or twice in the lab, so researchers worldwide will be able to create it.”

Professor Hutmacher said the new hydrogel could be used as a ‘bioink’ to print 3D ‘microenvironments’ or models of a tumour to test different anti-cancer drugs.

“We will be able to use this hydrogel infused with tumour cells to quickly create a number of models of patient-specific tumours.

“Instead of the sometimes hit and miss chemotherapy that affects every cell in the body this will allow us to test different anti-cancer drugs and different combinations of them all at once so that we can pinpoint an individualised treatment that will hit only the cancer cells.

“It will cut the process of finding a personalised treatment for each patient down to a week or two.” Because the hydrogel can be modified to mimic the firmness of cartilage or softness of breast tissue it can be used to create models for all types of cancer and also for research on stem cells and tissue engineering.

The IHBI research team includes Dr Daniela Loessner, Associate Professor Travis Klein and PhD student Christoph Meinert. The study, Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms was published this week.

The new hydrogel discovery is part of Biofabrication Research led by Professor Hutmacher at IHBI, which launched the world’s first Master of Biofabrication, a dual Australian and European master degree.

“We are seeking more students for the masters course at IHBI from all science and technology disciplines,” Professor Hutmacher says.

“Biofabrication is the future of medicine. It is a multidisciplinary area of research that requires an understanding of chemistry, physics, biology, medicine, robotics and computer science and we welcome graduates from any of these fields to apply for the master degree.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160321110301.htm  Original web page at Science Daily

Categories
News

* Functional heart muscle regenerated in decellularized human hearts

A partially recellularized human whole-heart cardiac scaffold, reseeded with human cardiomyocytes derived from induced pluripotent stem cells, being cultured in a bioreactor that delivers a nutrient solution and replicates some of the environmental conditions around a living heart.

Massachusetts General Hospital (MGH) researchers have taken some initial steps toward the creation of bioengineered human hearts using donor hearts stripped of components that would generate an immune response and cardiac muscle cells generated from induced pluripotent stem cells (iPSCs), which could come from a potential recipient. The investigators described their accomplishments — which include developing an automated bioreactor system capable of supporting a whole human heart during the recellularization process — earlier this year in Circulation Research.

“Generating functional cardiac tissue involves meeting several challenges,” says Jacques Guyette, PhD, of the MGH Center for Regenerative Medicine (CRM), lead author of the report. “These include providing a structural scaffold that is able to support cardiac function, a supply of specialized cardiac cells, and a supportive environment in which cells can repopulate the scaffold to form mature tissue capable of handling complex cardiac functions.”

The research team is led by Harald Ott, MD, of the MGH CRM and the Department of Surgery, senior author of the paper. In 2008, Ott developed a procedure for stripping the living cells from a donor organ with a detergent solution and then repopulating the remaining extracellular matrix scaffold with organ-appropriate types of cells. Since then his team has used the approach to generate functional rat kidneys and lungs and has decellularized large-animal hearts, lungs and kidneys. This report is the first to conduct a detailed analysis of the matrix scaffold remaining after decellularization of whole human hearts, along with recellularization of the cardiac matrix in three-dimensional and whole-heart formats.

The study included 73 human hearts that had been donated through the New England Organ Bank, determined to be unsuitable for transplantation and recovered under research consent. Using a scaled-up version of the process originally developed in rat hearts, the team decellularized hearts from both brain-dead donors and from those who had undergone cardiac death. Detailed characterization of the remaining cardiac scaffolds confirmed a high retention of matrix proteins and structure free of cardiac cells, the preservation of coronary vascular and microvascular structures, as well as freedom from human leukocyte antigens that could induce rejection. There was little difference between the reactions of organs from the two donor groups to the complex decellularization process.

Instead of using genetic manipulation to generate iPSCs from adult cells, the team used a newer method to reprogram skin cells with messenger RNA factors, which should be both more efficient and less likely to run into regulatory hurdles. They then induced the pluripotent cells to differentiate into cardiac muscle cells or cardiomyocytes, documenting patterns of gene expression that reflected developmental milestones and generating cells in sufficient quantity for possible clinical application. Cardiomyocytes were then reseeded into three-dimensional matrix tissue, first into thin matrix slices and then into 15 mm fibers, which developed into spontaneously contracting tissue after several days in culture.

The last step reflected the first regeneration of human heart muscle from pluripotent stem cells within a cell-free, human whole-heart matrix. The team delivered about 500 million iPSC-derived cardiomyocytes into the left ventricular wall of decellularized hearts. The organs were mounted for 14 days in an automated bioreactor system developed by the MGH team that both perfused the organ with nutrient solution and applied environmental stressors such as ventricular pressure to reproduce conditions within a living heart. Analysis of the regenerated tissue found dense regions of iPSC-derived cells that had the appearance of immature cardiac muscle tissue and demonstrated functional contraction in response to electrical stimulation.

“Regenerating a whole heart is most certainly a long-term goal that is several years away, so we are currently working on engineering a functional myocardial patch that could replace cardiac tissue damaged due a heart attack or heart failure,” says Guyette. “Among the next steps that we are pursuing are improving methods to generate even more cardiac cells — recellularizing a whole heart would take tens of billions — optimizing bioreactor-based culture techniques to improve the maturation and function of engineered cardiac tissue, and electronically integrating regenerated tissue to function within the recipient’s heart.”

Team leader Ott, an assistant professor of Surgery at Harvard Medical School, adds, “Generating personalized functional myocardium from patient-derived cells is an important step towards novel device-engineering strategies and will potentially enable patient-specific disease modeling and therapeutic discovery. Our team is excited to further develop both of these strategies in future projects.”

https://www.sciencedaily.com/   Science Daily

https://www.sciencedaily.com/releases/2016/03/160311110726.htm  Original web page at Science Daily

Categories
News

* Popular stem cell techniques deemed safe; unlikely to pass on cancer-causing mutations

A new study led by scientists at The Scripps Research Institute (TSRI) and the J. Craig Venter Institute (JCVI) shows that the act of creating pluripotent stem cells for clinical use is unlikely to pass on cancer-causing mutations to patients.

The research, published February 19, 2016 in the journal Nature Communications, is an important step in assessing patient safety in the rapidly developing field of stem cell therapies.

The new study focused on the safety of using induced pluripotent stem cells (iPSCs) in human patients. Because iPSCs can differentiate into any kind of cell in the body, they hold potential for repairing damage from injuries or diseases such as Parkinson’s and multiple sclerosis.

“We wanted to know whether reprogramming cells would make the cells prone to mutations,” said Jeanne Loring, professor of developmental neurobiology at TSRI and co-leader of the new study with Nicholas J. Schork, professor and director of human biology at JCVI. “The answer is ‘no.'”

“The safety of patients comes first, and our study is one of the first to address the safety concerns about iPSC-based cell replacement strategies and hopefully will spark further interest,” added Schork.

To make an iPSC, scientists must reprogram an adult cell, such as a skin cell, to express a different set of genes, which can be accomplished using viruses as delivery vehicles or with molecules called messenger RNAs (mRNAs).

The researchers looked at three popular methods of iPSC production (integrating retroviral vectors, non-integrating Sendai virus and synthetic mRNAs), assessing each for the potential to trigger cancer-causing mutations. While the researchers noted some minor alterations in the iPSCs, none of the methods led to significant mutations. The researchers repeated the experiments two more times and again found no significant risk. “The methods we’re using to make pluripotent stem cells are safe,” said Loring.

The scientists do warn that even though iPSCs don’t gain cancer-causing mutations during reprogramming, potentially harmful mutations can accumulate later on as iPSCs multiply in lab cultures. Loring said scientists must analyze their cells for these mutations before using them in therapies.

“We need to move on to developing these cells for clinical applications,” said Loring. “The quality control we’re recommending is to use genomic methods to thoroughly characterize the cells before you put them into people.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/02/160219111215.htm  Original web page at Science Daily

Categories
News

Biotech giant publishes failures to confirm high-profile science

A biotechnology firm is releasing data on three failed efforts to confirm findings in high-profile scientific journals — details that the industry usually keeps secret.

Amgen, headquartered in Thousand Oaks, California, says that it hopes the move will encourage others in industry and academia to describe their own replication attempts, and thus help the scientific community to get to the bottom of work that other labs are having trouble verifying.

The data are posted online at a newly launched channel dedicated to quickly publishing efforts to confirm scientific findings. The ‘Preclinical Reproducibility and Robustness’ channel is hosted by F1000Research, the publishing platform of London-based publishers Faculty of 1000 (F1000). Scientists who are concerned about the irreproducibility of preclinical research say that they welcome the initiative — but are not sure whether it will gain traction.

The idea emerged from discussions at a meeting focused on improving scientific integrity, hosted by the US National Academy of Sciences in 2015. Sasha Kamb, who leads research discovery at Amgen, said that his company’s scientists have in many instances tried and failed to reproduce academic studies, but that it takes too much time and effort to publish these accounts through conventional peer-review procedures.

Bruce Alberts, a former editor-in-chief of Science who sits on F1000Research’s advisory board, suggested that Kamb try the faster F1000 route — an open-science publishing model in which submitted studies are posted online (for a fee that ranges from US$150 to $1000) before undergoing peer review; submissions are subject to checks by F1000 editors to ensure that data are freely available and that methods and reagents are adequately described.

“The idea is to get the data out and get it critically looked at,” Alberts says. The editors then invite open peer review of the studies. If reviewers recommend the work, it is indexed in databases such as PubMed and Scopus.

F1000, in turn, has created a designated channel for these studies in the hope that they will garner attention, give credit to researchers doing careful confirmatory experiments and provide a place where the original researchers of a study and other scientists can discuss reasons behind different outcomes.

In 2012, Amgen researchers made headlines when they declared that they had been unable to reproduce the findings in 47 of 53 ‘landmark’ cancer papers. Those papers were never identified — partly because of confidentiality concerns — and there are no plans to release details now either, says Kamb, who was not involved with that publication. He says that he prefers to focus on more-recent publications.

The three studies that Amgen has posted deliberately do not make a detailed comparison of their results to previous papers, says Kamb. “We don’t want to make strong conclusions that someone else’s work is wrong with a capital W,” he says.

One study adds to existing criticism of a Science paper that suggested that a cancer drug might be a potential treatment for Alzheimer’s disease; a second counters earlier findings (including some by Amgen researchers) connecting a gene to insulin sensitivity in mice, and a third counters a Nature paper reporting that inhibiting one particular protein could enhance degradation of other proteins associated with neurodegenerative diseases.

“We believe that interested scientists can look at our methods and results and draw their own conclusions,” Kamb says. Amgen researchers did not contact the original authors when they conducted their studies, he says, but future postings could be collaborative.

Right now, the main way that the scientific community spreads the word about irreproducible research is through innuendo, which is inefficient and unfair to the original researchers, says Ricardo Dolmetsch, global head of neuroscience at Novartis’s Institutes for Biomedical Research in Cambridge, Massachusetts. “Anything we can do to improve the ratio of signal to noise in the literature is very welcome,” he says.

The F1000 initiative is useful, but previous efforts have tried and failed to encourage the reporting of replications and negative results, cautions John Ioannidis, who studies scientific robustness at California’s Stanford University. That is because, in general, the scientific community undervalues such work, he says.

But Kamb says that he has spoken with several industry leaders who have expressed support, and he hopes that they will contribute eventually. Roger Perlmutter, head of research and development at pharmaceutical giant Merck, says his colleagues can participate in the channel “at their own discretion”. Morgan Sheng, a vice-president at biotechnology company Genentech in South San Francisco, says he can forsee his company’s scientists submitting data to the venture too.

“I believe the main risk of a publication venue like the F1000 channel is that it becomes a place for “bashing” good science, because biological experiments are complex and beset by many variables that are hard to control. Non-replication does not necessarily mean ‘not true’,” Sheng adds. He says the site should be careful to emphasize publication of positive replication data as well.

Academic researchers are unlikely to risk alienating their peers by publishing disconfirming results, predicts Elizabeth Iorns, head of Science Exchange in Palo Alto, California. Her firm provides an online marketplace where scientists can offer to do others’ experiments, which she used to launch a reproducibility initiative in 2012.

But providing industry scientists with a low-barrier way to share their attempts might prove a winning strategy, she says. “Hopefully, the awareness of the reproducibility issue has been raised such that people are no longer afraid to talk about it.”

Nature doi:10.1038/nature.2016.19269

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/biotech-giant-publishes-failures-to-confirm-high-profile-science-1.19269  Original web page at Nature

Categories
News

Legal tussle delays launch of huge toxicity database

A database of the toxicity of nearly 10,000 chemicals might reduce the need for animal safety-testing. A giant database on the health risks of nearly 10,000 chemicals will make it easier to predict the toxicity of tens of thousands of consumer products for which no data exist, say researchers. But a legal disagreement means they haven’t yet been able to make the database public, as they had hoped to do.

“This has the potential to save millions of animals and reduce testing costs by hundreds of millions,” says Thomas Hartung, a toxicologist at Johns Hopkins University in Baltimore, Maryland, who led the team that created the database. He describes his work in papers published on 11 February in Alternatives to Animal Experiments.

The index is built from a mountain of safety data collected over the past decade by the European Chemicals Agency (ECHA) in Helsinki, under a 2006 law known as REACH (registration, evaluation, authorization and restriction of chemicals). The information is already public, but not held in an easy-to-analyse format — so Hartung’s team developed software that extracted it and converted it into a searchable database.

But the ECHA says that it has exclusive rights to the information, and that Hartung did not gain the specific permission he needed from the agency in order to duplicate it. For the moment, Hartung has agreed to hold off making his team’s database public.

With the database, Hartung hopes that companies and regulators will find it easier to infer the toxic effects of untested substances by comparing them with structurally or biologically similar chemicals with known effects — a method called read-across.

Thomas Hartung has long promoted alternatives to animal safety-tests. That concept is already popular among chemical companies that seek alternatives to safety tests on animals, says Markus Wahl, a regulatory toxicologist at chemicals producer BASF in Ludwigshafen, Germany. The database will provide “helpful supporting evidence”, he says, but he adds that European regulators accept the results of read-across (in place of animal-safety tests) only occasionally. Hartung, a long-time promoter of alternatives to animal-based safety testing, hopes to change that.

A spokesperson for the ECHA says that read-across is a “good approach” for checking relatively simple concerns such as harmful effects to skin and eyes — but that it “proves to be challenging” for complex issues such as the effects of repeated exposure to chemicals. “Companies quite often fail to substantiate why the read-across is scientifically justified,” the agency says.

Hartung argues that the database will strengthen the scientific case for read-across, because the certainty of the comparison “increases with the extent and quality of data,” he says. The data might also prove very useful to US regulators, as the country’s lawmakers attempt to tighten legislation governing the safe use of chemicals. Currently, chemicals can go on the US market with little regulatory scrutiny.

Analysis of the database has shown that some animal tests are woefully irreproducible, Hartung adds. The Draize eye test, for example, in which chemicals are applied to rabbits’ eyes to check for harmful effects, is a “big lottery”, he says. The test, in use for decades, has been widely criticized for producing inconsistent results and raising animal-welfare concerns, but the Johns Hopkins team analysed 9,700 Draize results from the ECHA data to quantify the problem. The results, published alongside the description of the database, suggest that substances found to cause serious irreversible eye damage in one test have a 10% chance of being found harmless in a subsequent test. By contrast, substances found to cause reversible irritation to rabbits’ eyes have nearly a 60% chance of being found harmless in a later test.

Hartung says that numerous researchers have expressed interest in mining the database, including the US Environmental Protection Agency, the US National Institutes of Health and some academic and industry groups.

But the database has already run into legal trouble with the ECHA. Information on the ECHA’s website is “proprietary”, the agency says, and “may be subject to intellectual property rights or copyright” belonging to the chemical companies. “This is not a parochial or bureaucratic requirement,” a spokesperson added: the ECHA is “keen” to see the data being used, but says that it also needs to protect the rights of the companies that own the data.

Hartung counters that the research “makes use only of the publicly available data”, and that the agency shouldn’t prohibit their use for academic enquiry. He has agreed to delay making the database public until he gets the specific permission he needs from the ECHA, but it is not clear how long that will take.

Nature doi:10.1038/nature.2016.19365

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/legal-tussle-delays-launch-of-huge-toxicity-database-1.19365  Original web page at Nature

Categories
News

Researchers create ‘mini-brains’ in lab to study neurological diseases

Researchers at the Johns Hopkins Bloomberg School of Public Health say they have developed tiny “mini-brains” made up of many of the neurons and cells of the human brain — and even some of its functionality — and which can be replicated on a large scale.

The researchers say that the creation of these “mini-brains,” which will be discussed at the American Association for the Advancement of Science conference in Washington, DC on Feb. 12 at a press briefing and in a session on Feb. 13, could dramatically change how new drugs are tested for effectiveness and safety, taking the place of the hundreds of thousands of animals used for neurological scientific research in the United States. Performing research using these three-dimensional “mini-brains” — balls of brain cells that grow and form brain-like structures on their own over the course of eight weeks — should be superior to studying mice and rats because they are derived from human cells instead of rodents, they say.

“Ninety-five percent of drugs that look promising when tested in animal models fail once they are tested in humans at great expense of time and money,” says study leader Thomas Hartung, MD, PhD, the Doerenkamp-Zbinden Professor and Chair for Evidence-based Toxicology at the Bloomberg School. “While rodent models have been useful, we are not 150-pound rats. And even though we are not balls of cells either, you can often get much better information from these balls of cells than from rodents.

“We believe that the future of brain research will include less reliance on animals, more reliance on human, cell-based models.”

Hartung and his colleagues created the brains using what are known as induced pluripotent stem cells (iPSCs). These are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state and then are stimulated to grow into brain cells. Cells from the skin of several healthy adults were used to create the mini-brains, but Hartung says that cells from people with certain genetic traits or certain diseases can be used to create brains to study various types of pharmaceuticals. He says the brains can be used to study Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and even autism. Projects to study viral infections, trauma and stroke have been started.

Hartung’s mini-brains are very small — at 350 micrometers in diameter, or about the size of the eye of a housefly, they are just visible to the human eye — and hundreds to thousands of exact copies can be produced in each batch. One hundred of them can grow easily in the same petri dish in the lab. After cultivating the mini-brains for about two months, the brains developed four types of neurons and two types of support cells: astrocytes and oligodendrocytes, the latter of which go on to create myelin, which insulates the neuron’s axons and allows them to communicate faster.

The researchers could watch the myelin developing and could see it begin to sheath the axons. The brains even showed spontaneous electrophysiological activity, which could be recorded with electrodes, similar to an electroencephalogram, also known as EEG. To test them, the researchers placed a mini-brain on an array of electrodes and listened to the spontaneous electrical communication of the neurons as test drugs were added.

“We don’t have the first brain model nor are we claiming to have the best one,” says Hartung, who also directs the School’s Center for Alternatives to Animal Testing. “But this is the most standardized one. And when testing drugs, it is imperative that the cells being studied are as similar as possible to ensure the most comparable and accurate results.”

Hartung is applying for a patent for the mini-brains and is also developing a commercial entity called ORGANOME to produce them. He hopes production can begin in 2016. He says they are easily reproducible and hopes to see them used by scientists in as many labs as possible. “Only when we can have brain models like this in any lab at any time will we be able to replace animal testing on a large scale,” he says.

https://www.sciencedaily.com/   Science Daily

https://www.sciencedaily.com/releases/2016/02/160212163901.htm  Original web page at Science Daily

Categories
News

* Microchip used to build a first-ever artificial kidney

Vanderbilt University Medical Center nephrologist and associate professor of medicine Dr. William H. Fissell IV, is making major progress on a first-of-its kind device to free kidney patients from dialysis. He is building an implantable artificial kidney with microchip filters and living kidney cells that will be powered by a patient’s own heart.

“We are creating a bio-hybrid device that can mimic a kidney to remove enough waste products, salt and water to keep a patient off dialysis,” said Fissell. Fissell says the goal is to make it small enough, roughly the size of a soda can, to be implanted inside a patient’s body.

The key to the device is a microchip. “It’s called silicon nanotechnology. It uses the same processes that were developed by the microelectronics industry for computers,” said Fissell.

The chips are affordable, precise and make ideal filters. Fissell and his team are designing each pore in the filter one by one based on what they want that pore to do. Each device will hold roughly fifteen microchips layered on top of each other. But the microchips have another essential role beyond filtering. “They’re also the scaffold in which living kidney cells will rest,” said Fissell.

Fissell and his team use live kidney cells that will grow on and around the microchip filters. The goal is for these cells to mimic the natural actions of the kidney.

“We can leverage Mother Nature’s 60 million years of research and development and use kidney cells that fortunately for us grow well in the lab dish, and grow them into a bioreactor of living cells that will be the only “Santa Claus” membrane in the world: the only membrane that will know which chemicals have been naughty and which have been nice. Then they can reabsorb the nutrients your body needs and discard the wastes your body desperately wants to get rid of,” said Fissell. Because this bio-hybrid device sits out of reach from the body’s immune response, it is protected from rejection.

“The issue is not one of immune compliance, of matching, like it is with an organ transplant,” said Fissell. The device operates naturally with a patient’s blood flow.

“Our challenge is to take blood in a blood vessel and push it through the device. We must transform that unsteady pulsating blood flow in the arteries and move it through an artificial device without clotting or damage. And that’s where Vanderbilt biomedical engineer Amanda Buck comes in. Buck is using fluid dynamics to see if there are certain regions in the device that might cause clotting.

“It’s fun to go in and work in a field that I love, fluid mechanics, and get to see it help somebody,” said Buck.

She uses computer models to refine the shape of the channels for the smoothest blood flow. Then they rapidly prototype the new design using 3-D printing and test it to make the blood flow as smoothly as possible.

Fissell says he has a long list of dialysis patients eager to join a future human trial. Pilot studies of the silicon filters could start in patients by the end of 2017.

“My patients are absolutely my heroes,” said Fissell. “They come back again and again and they accept a crushing burden of illness because they want to live. And they’re willing to put all of that at risk for the sake of another patient.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/02/160215124438.htm  Original web page at Science Daily

Categories
News

A new method to dramatically improve the sequencing of metagenomes

An international team of computer scientists developed a method that greatly improves researchers’ ability to sequence the DNA of organisms that can’t be cultured in the lab, such as microbes living in the human gut or bacteria living in the depths of the ocean. They published their work in the Feb. 1 issue of Nature Methods.

The method, called TruSPADES, generates via computer so-called Synthetic Long Reads, segments that are about 10,000 base pairs of the genome, from the commonly used short reads of just 300 base pairs produced by machines from San Diego-based Illumina.

Using Synthetic Long Reads instead of short reads to assemble a genome is like using entire chapters rather than single sentences to assemble a book, researchers said. So there is a strong incentive to improve sequencing with long reads.

“This is the next generation of sequencing technologies,” said Pavel Pevzner, a professor of computer science at the University of California, and the lead author on the study. “It will make a significant impact on the practice of metagenomics sequencing.”

Currently, the leaders in the long-read sequencing market, Pacific Biosciences and Oxford Nanopore, generate long reads that can be inaccurate and difficult to use in complex sequencing problems, such as assembling metagenomes–whole colonies of microbes sampled from their natural environment. By contrast, the Synthetic Long Reads are 100 times more accurate and can be rapidly generated on a massive scale to cover a large fraction of bacteria in metagenomes.

To develop their new method, researchers took the shorter reads, 100 to 300 base pairs, equipped with barcodes. They then assembled the short reads together into Synthetic Long Reads by representing them using a de Brujin graph, a method often used in short read sequencing. The graph allows researchers to determine which reads are connected together, resulting in the longer and more accurate Synthetic Long Reads.

The next step is to apply this method to the study of various microbial communities ranging from human to marine microbiomes. Pevzner and co-author Anton Bankevich from St. Petersburg State University, are working with Christopher Dupont, a researcher at the J. Craig Venter Institute, to do just that.

Metagenomics is especially challenging because researchers do not study a single species of bacteria but hundreds of them that live together in a community. When they extract a sample from the community and sequence it, they end up with bits of bacterial genomes from all the organisms in the community. It’s very much like trying to solve hundreds of puzzles without knowing which pieces belong to which puzzle. TruSPADES and Synthetic Long Reads will help researchers solve these puzzles.

“This method gives us better results at a much smaller cost,” said Dupont. “We are now assembling genomes for organisms we didn’t even know existed.”

http://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/02/160216181453.htm  Original web page at Science Daily

Categories
News

Completely new kind of polymer could lead to artificial muscles, self-repairing materials

Imagine a polymer with removable parts that can deliver something to the environment and then be chemically regenerated to function again. Or a polymer that can lift weights, contracting and expanding the way muscles do.

These functions require polymers with both rigid and soft nano-sized compartments with extremely different properties that are organized in specific ways. A completely new hybrid polymer of this type has been developed by Northwestern University researchers that might one day be used in artificial muscles or other life-like materials; for delivery of drugs, biomolecules or other chemicals; in materials with self-repair capability; and for replaceable energy sources.

“We have created a surprising new polymer with nano-sized compartments that can be removed and chemically regenerated multiple times,” said materials scientist Samuel I. Stupp, the senior author of the study.

“Some of the nanoscale compartments contain rigid conventional polymers, but others contain the so-called supramolecular polymers, which can respond rapidly to stimuli, be delivered to the environment and then be easily regenerated again in the same locations. The supramolecular soft compartments could be animated to generate polymers with the functions we see in living things,” he said.

Stupp is director of Northwestern’s Simpson Querrey Institute for BioNanotechnology. He is a leader in the fields of nanoscience and supramolecular self-assembly, the strategy used by biology to create highly functional ordered structures.

The hybrid polymer cleverly combines the two types of known polymers: those formed with strong covalent bonds and those formed with weak non-covalent bonds, well known as “supramolecular polymers.” The integrated polymer offers two distinct “compartments” with which chemists and materials scientists can work to provide useful features.

The study is published in the Jan. 29 issue of Science. The paper is titled “Simultaneous covalent and noncovalent hybrid polymerizations.”

“Our discovery could transform the world of polymers and start a third chapter in their history: that of the ‘hybrid polymer,'” Stupp said. “This would follow the first chapter of broadly useful covalent polymers, then the more recent emerging class of supramolecular polymers.

“We can create active or responsive materials not known previously by taking advantage of the compartments with weak non-covalent bonds, which should be highly dynamic like living things. Some forms of these polymers now under development in my laboratory behave like artificial muscles,” he said.

Polymers get their power and features from their structure at the nanoscale. The covalent rigid skeleton of Stupp’s first hybrid polymer has a cross-section shaped like a ninja star — a hard core with arms spiraling out. In between the arms is the softer “life force” material. This is the area that can be animated, refreshed and recharged, features that could be useful in a range of valuable applications.

“The fascinating chemistry of the hybrid polymers is that growing the two types of polymers simultaneously generates a structure that is completely different from the two grown alone,” Stupp said. “I can envision this new material being a super-smart patch for drug delivery, where you load the patch with different medications, and then reload it in the exact same compartments when the medicine is gone.”

Stupp also is the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering and holds appointments in Northwestern University Feinberg School of Medicine, the McCormick School of Engineering and Applied Science and the Weinberg College of Arts and Sciences.

Stupp and his research team also discovered that the covalent polymerization that forms the rigid compartment is “catalyzed” by the supramolecular polymerization, thus yielding much higher molecular weight polymers.

The strongly bonded covalent compartment provides the skeleton, and the weakly bonded supramolecular compartment can wear away or be used up, depending on its function, and then be regenerated by adding small molecules. After the simultaneous polymerizations of covalent and non-covalent bonds, the two compartments end up bonded to each other, yielding a very long, perfectly shaped cylindrical filament.

To better understand the hybrid’s underlying chemistry, Stupp and his team worked with George C. Schatz, a world-renowned theoretician and a Charles E. and Emma H. Morrison Professor of Chemistry at Northwestern. Schatz’s computer simulations showed the two types of compartments are nicely integrated with hydrogen bonds, which are bonds that can be broken. Schatz is a co-author of the study.

“This is a remarkable achievement in making polymers in a totally new way — simultaneously controlling both their chemistry and how their molecules come together,” said Andy Lovinger, a materials science program director at the National Science Foundation, which funded this research.

“We’re just at the very start of this process, but further down the road it could potentially lead to materials with unique properties — such as disassembling and reassembling themselves — which could have a broad range of applications,” Lovinger said.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2016/01/160128154827.htm  Original web page at Science Daily

Categories
News

* Dog domestication may have increased harmful genetic changes, biologists report

The domestication of dogs may have inadvertently caused harmful  genetic changes, a UCLA-led study suggests. Domesticating dogs from gray wolves more than 15,000 years ago involved artificial selection and inbreeding, but the effects of these processes on dog genomes have been little-studied.

UCLA researchers analyzed the complete genome sequences of 19 wolves; 25 wild dogs from 10 different countries; and 46 domesticated dogs from 34 different breeds. They found that domestication may have led to a rise in the number of harmful genetic changes in dogs, likely as a result of temporary reductions in population size known as bottlenecks.

“Population bottlenecks tied to domestication, rather than recent inbreeding, likely led to an increased frequency of deleterious genetic variations in dogs,” said Kirk Lohmueller, senior author of the research and assistant professor of ecology and evolutionary biology in the UCLA College.

“Our research suggests that such variants may have piggybacked onto positively selected regions, which were also enriched in disease-related genes,” Lohmueller said. “Thus, the use of small populations artificially bred for desired traits, such as smaller body size or coat color, may have led to an accumulation of harmful genetic variations in dogs.”

Such variations, Lohmueller said, could potentially lead to a number of different developmental disorders and other health risks.

Selective breeding programs, particularly those aimed at conserving rare and endangered species, may need to include and maintain large populations to minimize the inadvertent enrichment of harmful genetic changes, he said.

The research was published recently in the journal Proceedings of the National Academy of Sciences.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2016/01/160111162701.htm  Original web page at Science Daily

Categories
Cartoons News

First puppies born by in vitro fertilization

cartoon_11-08-2015

First puppies born by in vitro fertilization
VetScite News, January 13, 2016

Categories
News

* First puppies born by in vitro fertilization

For the first time, a litter of puppies was born by in vitro fertilization, thanks to work by Cornell University researchers. The breakthrough, described in a study to be published online Dec. 9 in the journal Public Library of Science ONE, opens the door for conserving endangered canid species, using gene-editing technologies to eradicate heritable diseases in dogs and for study of genetic diseases. Canines share more than 350 similar heritable disorders and traits with humans, almost twice the number as any other species.

Nineteen embryos were transferred to the host female dog, who gave birth to seven healthy puppies, two from a beagle mother and a cocker spaniel father, and five from two pairings of beagle fathers and mothers.

“Since the mid-1970s, people have been trying to do this in a dog and have been unsuccessful,” said Alex Travis, associate professor of reproductive biology in the Baker Institute for Animal Health in Cornell’s College of Veterinary Medicine.

Jennifer Nagashima, a graduate student in Travis’ lab and the first to enroll in the Joint Graduate Training Program between the Smithsonian Conservation Biology Institute and Cornell’s Atkinson Center for a Sustainable Future, is the paper’s first author.

For successful in vitro fertilization, researchers must fertilize a mature egg with a sperm in a lab, to produce an embryo. They must then return the embryo into a host female at the right time in her reproductive cycle.

The first challenge was to collect mature eggs from the female oviduct. The researchers first tried to use eggs that were in the same stage of cell maturation as other animals, but since dogs’ reproductive cycles differ from other mammals, those eggs failed to fertilize. Through experimentation, Nagashima and colleagues found if they left the egg in the oviduct one more day, the eggs reached a stage where fertilization was greatly improved.

The second challenge was that the female tract prepares sperm for fertilization, requiring researchers to simulate those conditions in the lab. Nagashima and Skylar Sylveste, found that by adding magnesium to the cell culture, it properly prepared the sperm. “We made those two changes, and now we achieve success in fertilization rates at 80 to 90 percent,” Travis said.

The final challenge for the researchers was freezing the embryos. Travis and colleagues delivered Klondike, the first puppy born from a frozen embryo in the Western Hemisphere in 2013. Freezing the embryos allowed the researchers to insert them into the recipient’s oviducts (called Fallopian tubes in humans) at the right time in her reproductive cycle, which occurs only once or twice a year.

The findings have wide implications for wildlife conservation because, Travis said, “We can freeze and bank sperm, and use it for artificial insemination. We can also freeze oocytes, but in the absence of in vitro fertilization, we couldn’t use them. Now we can use this technique to conserve the genetics of endangered species.”

In vitro fertilization allows conservationists to store semen and eggs and bring their genes back into the gene pool in captive populations. In addition to endangered species, this can also be used to preserve rare breeds of show and working dogs.

With new genome editing techniques, researchers may one day remove genetic diseases and traits in an embryo, ridding dogs of heritable diseases. While selecting for desired traits, inbreeding has also led to detrimental genetic baggage. Different breeds are predisposed to different diseases; Golden retrievers are likely to develop lymphoma, while Dalmatians carry a gene that predisposes them to blockage with urinary stones.

“With a combination of gene editing techniques and IVF, we can potentially prevent genetic disease before it starts,” Travis said. Finally, since dogs and humans share so many diseases, dogs now offer a “powerful tool for understanding the genetic basis of diseases,” Travis said.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/12/151209183500.htm  Original web page at Science Daily

Categories
News

* Nanotechnology advances could pave way for implantable artificial kidney

A surgically implantable, artificial kidney could be a promising alternative to kidney transplantation or dialysis for people with end stage renal disease (ESRD). Currently, more than 20 million Americans have kidney diseases, and more than 600,000 patients are receiving treatment for ESRD. U.S. government statistics indicate kidney care costs the U.S. health care system $40 billion annually, accounting for more than 6 percent of Medicare spending.

“We aim to conduct clinical trials on an implantable, engineered organ in this decade, and we are coordinating our efforts with both the NIH and the U.S. Food and Drug Administration,” said Shuvo Roy, PhD, a UC San Francisco bioengineer who led the research together with Vanderbilt University nephrologist William Fissell, MD. Roy is the technical director of The Kidney Project at UCSF, a multi-institutional collaboration that has prototyped and begun testing key components of the coffee-cup-sized device, which mimics functions of the human kidney.

One component of the new artificial kidney is a silicon nanofilter to remove toxins, salts, some small molecules, and water from the blood. Roy’s research team designed it based on manufacturing methods used in the production of semiconductor electronics and microelectromechanical systems. The new silicon nanofilters offer several advantages — including more uniform pore size — over filters now used in dialysis machines, according to Roy. The silicon nanofilter is designed to function on blood pressure alone and without a pump or electrical power. Fissell, associate professor in the Department of Medicine at Vanderbilt and medical director for The Kidney Project, said the project’s goal is to create a permanent solution to the scarcity problem in organ transplantation. “We are increasing the options for people with chronic kidney disease who would otherwise be forced onto dialysis,” Fissell added.

The artificial kidney being developed by Roy and Fissell is designed to be connected internally to the patient’s blood supply and bladder and implanted near the patient’s own kidneys, which are not removed. Along with Roy at UCSF and Fissell at Vanderbilt, a national team of scientists and engineers at universities and small businesses are working toward making the implantable artificial kidney available to patients.

In September the project was designated for inclusion in the FDA’s new Expedited Access Pathway program to speed development, evaluation, and review of medical devices that meet major unmet needs in fighting life-threatening or irreversibly debilitating diseases.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/11/151110145150.htm  Original web page at Science Daily

Categories
News

Test tube foals that could help ensure rare breed survival

The recent birth of two test tube foals in the UK, as part of a collaborative project conducted by leading fertility experts, could help benefit rare breed conservation and horses with fertility problems. The births mark the successful completion of a three-year program, the aim of which was to establish and offer advanced breeding methods that are not routinely available in the UK. The births mark the successful completion of a three-year program, led by the University of Liverpool, the University of Surrey and Twemlows Stud Farm. The aim of the project was to establish and offer advanced breeding methods that are not routinely available in the UK.

It is thought that these processes could have further use in breeds under threat of extinction and for valued horses that have died or in cases where mares or stallions have specific fertility problems.

One method, called intracytoplasmic sperm injection (ICSI), has the potential to allow greater numbers of offspring to be produced from individual mares and from stallions where sperm samples are limited, allowing breeds to continue in larger numbers. Importantly, this method could allow the embryos of rare breeds to be ‘frozen’, creating a safety net of ‘reserve animals’ should anything threaten the existing stock.

Niamh Lewis, a veterinarian researcher at the University of Liverpool, who managed the project said: “These are complex methods which are currently offered by only a very few centres worldwide. The ability to perform these techniques reliably offers new hope to help overcome various fertility issues in stallions and also provides opportunities to create offspring from valuable mares who have died unexpectedly or cannot conceive in their own right.”

The foals were born using two different advanced breeding techniques. In June this year a foal named Twemlows Simba became the first foal in the UK to be born using Oocyte Transfer, a technique that involves oocytes (eggs) being collected from a donor mare and then transplanted into a surrogate female before being fertilised.

A second foal called Twemlows Little ICSI was born earlier this month using an ICSI. This technique is already used with great success for infertile human couples and involves a single sperm being injected into an egg through a thin glass pipette to create an embryo which is then transferred to a surrogate female. In this case the egg had been harvested from the ovary of a mare that died 11 months ago and was then matured in the laboratory ahead of the procedure. If rare breed embryos can be reliably frozen, as opposed to just semen as currently archived then, in case of a crisis, the breed could be resurrected by returning the embryos to surrogate mares.

Professor Caroline Argo from the University of Surrey, who was the academic lead for the project adds: “At the moment, we can freeze stallion sperm reliably but not horse eggs or embryos. However, ICSI embryos are smaller and more robust to the freezing process. Now that this method has proved successful, it could be possible to use it more routinely and widely for the purposes of conservation.”

The project was a Knowledge Transfer Partnership, jointly funded by the government’s Technology Strategy Board and Twemlows Stud Farm, Shropshire, and encompassed a major collaborative effort, which included working with consultant clinical embryologists in human medicine.

Mr Edward Matson of Twemlows Stud Farm said: “We have always strived to stay at the forefront of horse breeding and to offer our clients the most up to date techniques which are firmly centred on good science and focus on the welfare of their animals.

“The opportunity to collaborate with academic and clinical partners has allowed us to extend our service to include these advanced techniques. Until now, clients wishing to embark on these methods were largely dependent on shipping animals to overseas clinics.

Tom Beeston, CEO of the Rare Breeds Survival Trust, said: “Breeding numbers of all our native equine breeds continue to decline, if not halted soon our gene bank may be needed to reconstitute a breed, it really is that serious. Being able to freeze embryos as well as semen will mean we can do this completely and faster. This project is by far our best hope of being able to do this soon.”

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/10/151021135922.htm  Original web page at Science Daily

Categories
News

Artificial foam heart created

Cornell University researchers have developed a new lightweight and stretchable material with the consistency of memory foam that has potential for use in prosthetic body parts, artificial organs and soft robotics. The foam is unique because it can be formed and has connected pores that allow fluids to be pumped through it.

The polymer foam starts as a liquid that can be poured into a mold to create shapes, and because of the pathways for fluids, when air or liquid is pumped through it, the material moves and can change its length by 300 percent.

While applications for use inside the body require federal approval and testing, Cornell researchers are close to making prosthetic body parts with the so-called “elastomer foam.

“We are currently pretty far along for making a prosthetic hand this way,” said Rob Shepherd, assistant professor of mechanical and aerospace engineering, and senior author of a paper appearing online and in an upcoming issue of the journal Advanced Materials. Benjamin Mac Murray, a graduate student in Shepherd’s lab, is the paper’s first author.

In the paper, the researchers demonstrated a pump they made into a heart, mimicking both shape and function. The researchers used carbon fiber and silicone on the outside to fashion a structure that expands at different rates on the surface — to make a spherical shape into an egg shape, for example, that would hold its form when inflated.

“This paper was about exploring the effect of porosity on the actuator, but now we would like to make the foam actuators faster and with higher strength, so we can apply more force. We are also focusing on biocompatibility,” Shepherd said.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/10/151014204515.htm  Original web page at Science Daily

Categories
News

Investigators create complex kidney structures from human stem cells derived from adults

New technique offers model for studying disease, progress toward cell therapy. Researchers modeled kidney development and injury in kidney organoids (shown here), demonstrating that the organoid culture system can be used to study mechanisms of human kidney development and toxicity.

Investigators at Brigham and Women’s Hospital (BWH) and the Harvard Stem Cell Institute (HSCI) have established a highly efficient method for making kidney structures from stem cells that are derived from skin taken from patients. The kidney structures formed could be used to study abnormalities of kidney development, chronic kidney disease, the effects of toxic drugs, and be incorporated into bioengineered devices to treat patients with acute and chronic kidney injury. In the longer term, these methods could hasten progress toward replacing a damaged or diseased kidney with tissue derived from a patient’s own cells. These results were published in Nature Biotechnology this week.

“Kidneys are the most commonly transplanted organs, but demand far outweighs supply,” said co-corresponding author Ryuji Morizane, MD, PhD, associate biologist in BWH’s Renal Division. “We have converted skin cells to stem cells and developed a highly efficient process to convert these stem cells into kidney structures that resemble those found in a normal human kidney. We’re hopeful that this finding will pave the way for the future creation of kidney tissues that could function in a patient and eliminate the need for transplantation from a donor.”

Chronic kidney disease (CKD) affects 9 to11 percent of the U.S. adult population and is a serious public health problem worldwide. Central to the progression of CKD is the gradual and irreversible loss of nephrons, the individual functional units of the kidney. Patients with end-stage kidney disease benefit from treatments such as dialysis and kidney transplantation, but these approaches have several limitations, including the limited supply of compatible organ donors.

While the human kidney does have some capacity to repair itself after injury, it is not able to regenerate new nephrons. In previous studies, researchers have successfully differentiated stem cells into heart, liver, pancreas or nerve cells by adding certain chemicals, but kidney cells have proved challenging. Using normal kidney development as a roadmap, the BWH investigators developed an efficient method to create kidney precursor cells that self assemble into structures which mimic complex structures of the kidney. The research team further tested these organoids — three-dimensional organ structures grown in the lab — and found that they could be used to model kidney development and susceptibility of the kidney tissue to therapeutic drug toxicity. The kidney structures also have the potential to facilitate further studies of how abnormalities occur as the human kidney develops in the uterus and to establish models of disease where they can be used to test new therapies

“This new finding could hasten progress to model human disease, find new therapeutic agents, identify patient-specific susceptibility to toxicity of drugs and may one day result in replacement of human kidney tissue in patients with kidney disease from cells derived from that same patient,” said author Joseph V. Bonventre, chief of BWH’s Renal Division and Chief of BWH’s Division of Biomedical Engineering. “This approach is especially attractive because the tissues obtained would be ‘personalized’ and, because of their genetic identity to the patient from whom they were derived, this approach may ultimately lead to tissue replacement without the need for suppression of the immune system.”

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/10/151016142633.htm  Original web page at Science Daily

Categories
News

An accessible approach to making a mini-brain

If you need a working miniature brain — say for drug testing, to test neural tissue transplants, or to experiment with how stem cells work — a new paper describes how to build one with what the Brown University authors say is relative ease and low expense. The little balls of brain aren’t performing any cogitation, but they produce electrical signals and form their own neural connections — synapses — making them readily producible testbeds for neuroscience research, the authors said.

“We think of this as a way to have a better in vitro [lab] model that can maybe reduce animal use,” said graduate student Molly Boutin, co-lead author of the new paper in the journal Tissue Engineering: Part C. “A lot of the work that’s done right now is in two-dimensional culture, but this is an alternative that is much more relevant to the in vivo [living] scenario.”

Just a small sample of living tissue from a single rodent can make thousands of mini-brains, the researchers said. The recipe involves isolating and concentrating the desired cells with some centrifuge steps and using that refined sample to seed the cell culture in medium in an agarose spherical mold.

The mini-brains, about a third of a millimeter in diameter, are not the first or the most sophisticated working cell cultures of a central nervous system, the researchers acknowledged, but they require fewer steps to make and they use more readily available materials.

“The materials are easy to get and the mini-brains are simple to make,” said co-lead author Yu-Ting Dingle, who earned her Ph.D. at Brown in May 2015. She compared them to retail 3-D printers which have proliferated in recent years, bringing that once-rare technology to more of a mass market. “We could allow all kinds of labs to do this research.”

The spheres of brain tissue begin to form within a day after the cultures are seeded and have formed complex 3-D neural networks within two to three weeks, the paper shows

There are fixed costs, of course, but an approximate cost for each new mini-brain is on the order of $0.25, said study senior author Diane Hoffman-Kim, associate professor of molecular pharmacology, physiology and biotechnology and associate professor of engineering at Brown. “We knew it was a relatively high-throughput system, but even we were surprised at the low cost per mini-brain when we computed it,” Hoffman-Kim said

Hoffman-Kim’s lab collaborated with fellow biologists and bioengineers at Brown — faculty colleagues Julie Kauer, Jeffrey Morgan, and Eric Darling are all co-authors — to build the mini-brains. She wanted to develop a testbed for her lab’s basic biomedical research. She was interested, for example, in developing a model to test aspects of neural cell transplantation, as has been proposed to treat Parkinson’s disease. Boutin was interested in building working 3-D cell cultures to study how adult neural stem cells develop

Morgan’s Providence startup company, MicroTissues Inc., makes the 3-D tissue engineering molds used in the study

The method they developed yields mini-brains with several important properties:Diverse cell types: The cultures contain both inhibitory and excitatory neurons and several varieties of essential neural support cells called glia.

Electrically active: the neurons fire and spike and form synaptic connections, producing complex networks.3-D: Cells connect and communicate within a realistic geometry, rather than merely across a flat plane as in a 2-D culture.Natural density: Experiments showed that the mini-brains have a density of a few hundred thousand cells per cubic millimeter, which is similar to a natural rodent brain.

Physical structure: Cells in the mini-brain produce their own extracellular matrix, producing a tissue with the same mechanical properties (squishiness) as natural tissue. The cultures also don’t rely on foreign materials such as scaffolds of collagen.Longevity: In testing, cultured tissues live for at least a month.

Hoffman-Kim, who is affiliated with the Brown Institute for Brain Science and the Center for Biomedical Engineering, said she hopes the mini-brains might proliferate to many different labs, including those of researchers who have questions about neural tissue but not necessarily the degree of neuroscience and cell culture equipment required of other methods.

“If you are that person in that lab, we think you shouldn’t have to equip yourself with a microelectronics facility, and you shouldn’t have to do embryonic dissections in order to generate an in vitro model of the brain,” Hoffman-Kim said.

The paper’s other authors are Anda Chirila, Liane Livi, Nicholas Labriola, and Lorin Jakubek.

The National Science Foundation, the National Institutes of Health, the Brown Institute for Brain Science, and the U.S. Department of Education funded the research.

http://www.sciencedaily.com   Science Daily

http://www.sciencedaily.com/releases/2015/10/151001093854.htm  Original web page at Science Daily

Categories
News

Self-propelled powder designed to stop severe bleeding

UBC researchers have created the first self-propelled particles capable of delivering coagulants against the flow of blood to treat severe bleeding, a potentially huge advancement in trauma care.

“Bleeding is the number one killer of young people, and maternal death from postpartum hemorrhage can be as high as one in 50 births in low resource settings so these are extreme problems,” explains Christian Kastrup, an assistant professor in the Department of Biochemistry and Molecular Biology and the Michael Smith Laboratories at the University of British Columbia.

Traditional methods of halting severe bleeding are not very effective when the blood loss originates inside the body like the uterus, sinus or abdomen.

“People have developed hundreds of agents that can clot blood but the issue is that it’s hard to push these therapies against severe blood flow, especially far enough upstream to reach the leaking vessels. Here, for the first time, we’ve come up with an agent that can do that,” Kastrup said

Kastrup teamed up with a group of researchers, biochemical engineers and emergency physicians to develop simple, gas-generating calcium carbonate micro-particles that can be applied in powder form to stop critical bleeding. The particles work by releasing carbon dioxide gas, like antacid tablets, to propel them toward the source of bleeding. The carbonate forms porous micro particles that can bind with a clotting agent known as tranexamic acid, and transport it through wounds and deep into the damaged tissue

After studying and modeling the movement of the particles in vitro, the researchers confirmed their results using two animal models. Even in a scenario that mimicked a catastrophic event like a gunshot wound to a femoral artery, the particles proved highly effective in stopping the bleeding

While much more rigorous testing and development is needed to bring the agent to market, the particles could have a wide range of uses, from sinus operations to treating combat wounds.

“The area we’re really focusing on is postpartum hemorrhage: in the uterus, after childbirth where you can’t see the damaged vessels but you can put the powder into that area and the particles can propel and find those damaged vessels,” said Kastrup.

http://www.sciencedaily.com  Science Daily

http://www.sciencedaily.com/releases/2015/10/151002144909.htm  Original web page at Science Daily

Categories
News

Sensor could detect viruses, kill cancer cells

MIT biological engineers have developed a modular system of proteins that can detect a particular DNA sequence in a cell and then trigger a specific response, such as cell death.

This system can be customized to detect any DNA sequence in a mammalian cell and then trigger a desired response, including killing cancer cells or cells infected with a virus, the researchers say.

“There is a range of applications for which this could be important,” says James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science (IMES). “This allows you to readily design constructs that enable a programmed cell to both detect DNA and act on that detection, with a report system and/or a respond system.”

Collins is the senior author of a Sept. 21 Nature Methods paper describing the technology, which is based on a type of DNA-binding proteins known as zinc fingers. These proteins can be designed to recognize any DNA sequence.

“The technologies are out there to engineer proteins to bind to virtually any DNA sequence that you want,” says Shimyn Slomovic, an IMES postdoc and the paper’s lead author. “This is used in many ways, but not so much for detection. We felt that there was a lot of potential in harnessing this designable DNA-binding technology for detection.”

To create their new system, the researchers needed to link zinc fingers’ DNA-binding capability with a consequence — either turning on a fluorescent protein to reveal that the target DNA is present or generating another type of action inside the cell.

The researchers achieved this by exploiting a type of protein known as an “intein” — a short protein that can be inserted into a larger protein, splitting it into two pieces. The split protein pieces, known as “exteins,” only become functional once the intein removes itself while rejoining the two halves.

Collins and Slomovic decided to divide an intein in two and then attach each portion to a split extein half and a zinc finger protein. The zinc finger proteins are engineered to recognize adjacent DNA sequences within the targeted gene, so if they both find their sequences, the inteins line up and are then cut out, allowing the extein halves to rejoin and form a functional protein. The extein protein is a transcription factor designed to turn on any gene the researchers want.

In this paper, they linked green fluorescent protein (GFP) production to the zinc fingers’ recognition of a DNA sequence from an adenovirus, so that any cell infected with this virus would glow green. This approach could be used not only to reveal infected cells, but also to kill them. To achieve this, the researchers could program the system to produce proteins that alert immune cells to fight the infection, instead of GFP.

“Since this is modular, you can potentially evoke any response that you want,” Slomovic says. “You could program the cell to kill itself, or to secrete proteins that would allow the immune system to identify it as an enemy cell so the immune system would take care of it.”

The MIT researchers also deployed this system to kill cells by linking detection of the DNA target to production of an enzyme called NTR. This enzyme activates a harmless drug precursor called CB 1954, which the researchers added to the petri dish where the cells were growing. When activated by NTR, CB 1954 kills the cells.

Future versions of the system could be designed to bind to DNA sequences found in cancerous genes and then produce transcription factors that would activate the cells’ own programmed cell death pathways.

The researchers are now adapting this system to detect latent HIV proviruses, which remain dormant in some infected cells even after treatment. Learning more about such viruses could help scientists find ways to permanently eliminate them.

“Latent HIV provirus is pretty much the final barrier to curing AIDS, which currently is incurable simply because the provirus sequence is there, dormant, and there aren’t any ways to eradicate it,” Slomovic says.

While treating diseases using this system is likely many years away, it could be used much sooner as a research tool, Collins says. For example, scientists could use it to test whether genetic material has been successfully delivered to cells that scientists are trying to genetically alter. Cells that did not receive the new gene could be induced to undergo cell death, creating a pure population of the desired cells.

It could also be used to study chromosomal inversions and transpositions that occur in cancer cells, or to study the 3-D structure of normal chromosomes by testing whether two genes located far from each other on a chromosome fold in such a way that they end up next to each other, the researchers say.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/09/150921133837.htm  Original web page at Science Daily

Categories
News

New ‘Tissue Velcro’ could help repair damaged hearts

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together just like Velcro™. “One of the main advantages is the ease of use,” says biomedical engineer Professor Milica Radisic, who led the project. “We can build larger tissue structures immediately before they are needed, and disassemble them just as easily. I don’t know of any other technique that gives this ability.”

Growing heart muscle cells in the lab is nothing new. The problem is that too often, these cells don’t resemble those found in the body. Real heart cells grow in an environment replete with protein scaffolds and support cells that help shape them into long, lean beating machines. In contrast, lab-grown cells often lack these supports, and tend to be amorphous and weak. Radisic and her team focus on engineering artificial environments that more closely imitate what cells see in the body, resulting in tougher, more robust cells.

Two years ago, Radisic and her team invented the Biowire, in which heart cells grew around a silk suture, imitating the way real muscle fibres grow in the heart. “If you think of single fibre as a 1D structure, then the next step is to create a 2D structure and then assemble those into a 3D structure,” says Boyang Zhang a PhD candidate in Radisic’s lab. Zhang and Miles Montgomery, another PhD student in the lab, were co-lead authors on the current work, published today in Science Advances.

Zhang and his colleagues used a special polymer called POMaC to create a 2D mesh for the cells to grow around. It somewhat resembles a honeycomb in shape, except that the holes are not symmetrical, but rather wider in one direction than in another. Critically, this provides a template that causes the cells to line up together. When stimulated with an electrical current, the heart muscle cells contract together, causing the flexible polymer to bend.

Next the team bonded T-shaped posts on top of the honeycomb. When a second sheet is placed above, these posts act like tiny hooks, poking through the holes of honeycomb and clicking into place. The concept the same as the plastic hooks and loops of Velcro™, which itself is based on the burrs that plants use to hitch their seeds to passing animals.

Amazingly, the assembled sheets start to function almost immediately. “As soon as you click them together, they start beating, and when we apply electrical field stimulation, we see that they beat in synchrony,” says Radisic. The team has created layered tissues up to three sheets thick in a variety of configurations, including tiny checkerboards.

The ultimate goal of the project is to create artificial tissue that could be used to repair damaged hearts. The modular nature of the technology should make it easier to customize the graft to each patient. “If you had these little building blocks, you could build the tissue right at the surgery time to be whatever size that you require,” says Radisic. The polymer scaffold itself is biodegradable; within a few months it will gradually break down and be absorbed by the body.

Best of all, the technique is not limited to heart cells. “We use three different cell types in this paper; cardiomyocytes, fibroblasts and endothelial cells, but conceptually there is really no limitation,” says Radisic. That means that other researchers could use the scaffold to build layered structures that imitate a variety of tissues, livers to lungs. These artificial tissues could be used to test out new drugs in a realistic environment.

Moreover, the ability to assemble and disassemble them at will could enable scientists to get much more detailed information on cell response than is currently possible. “You could take middle layer out, to see what the cells look like,” says Radisic. “Then you could apply a molecule that will cause differentiation or proliferation or whatever you want, to just that layer. Then you could put it back into the tissue, to see how it interacts with the remaining layers.”

The next step is to test how well the system functions in vivo. Radisic and her team are collaborating with medical researchers in order to design implantation experiments that will take the project one step closer to the clinic.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/08/150828142946.htm  Original web page at Science Daily

Categories
News

Next-generation X-ray source fires up

Sweden’s MAX-IV laboratory will host the first two ‘fourth-generation’ light sources. Electrons have begun circulating in a synchrotron in Lund, Sweden, in what researchers hope marks the start of a new era for X-ray science.

Synchrotrons are particle accelerators that produce X-rays used in research ranging from structural biology to materials science. The next generation of this technology promises to lower the costs of X-ray-light sources around the world, whilst improving their performance and enabling experiments that were not possible before.

At 10 pm local time on 25 August the first bunches of electrons began circulating inside a new 528-meter-long, 3 gigaelectronvolt (GeV) machine at the MAX IV facility in Lund, project director Christoph Quitmann told Nature. MAX IV is the first ‘fourth-generation’ synchrotron in the world. “It means that something fatal has not happened early on,” says Robert Hettel, an accelerator physicist at SLAC National Accelerator Laboratory in Menlo Park, California. “Many rings in the past have had a hard time reaching this early milestone.”

“Getting the first beam is an absolutely crucial first step” in demonstrating fourth-generation technology, says Chris Jacobsen, an X-ray physicist at Northwestern University in Evanston, Illinois. He adds that MAX IV is “leading the world towards a new path in synchrotron light sources”.

In synchrotrons, bunches of electrons circulate at nearly the speed of light inside a ring-shaped vacuum tube. Powerful ‘bending’ magnets steer the electrons around the rings and ‘focusing’ magnets push them together against their mutual repulsion. The electrons then pass through special magnets that shake them sideways to produce pulses of X-rays, known as synchrotron radiation.

Fourth-generation light sources promise to squeeze the electrons into tighter bunches, leading to X-ray pulses that concentrate more photons into a tighter, brighter beam. This will enable researchers to do experiments that could take days on a third-generation machine in mere minutes, Jacobsen says.

Eventually, beams from fourth-generation machines could enable materials scientists to observe chemical reactions inside a battery as they happen, or structural biologists to reveal the structure of proteins from smaller protein crystals than those necessary at existing light sources.

The crucial innovation of the fourth-generation machines is to employ a narrower vacuum pipe to circulate electrons in. In MAX IV’s case, the pipe is 22 millimetres across, about half as wide as a typical current synchrotron. This makes it possible to get stronger magnetic fields using more compact bending and focusing magnets, which are also less expensive and can consume 10 times less electricity than third-generation systems due to their smaller size.

Keeping such a narrow pipe free of air would not have been possible with traditional high-vacuum pumps though. To do this MAX IV borrowed a technology from the Large Hadron Collider (LHC) near Geneva, Switzerland, which circulates protons rather than electrons. The LHC trick – now adopted by MAX IV – coats the inner surface of pipes with a special alloy that absorbs any molecules of air that happen to bounce around inside them

“The Swedes should be very proud of their innovative fabrication techniques, which lower the cost of making these machines,” said physicist Herman Winick, a veteran synchrotron builder at SLAC

In the next few weeks, the MAX IV team will have to test that they can circulate the large number of electrons that will be necessary to produce high-quality beams of X-rays, Hettel says. And in subsequent months, they will build eight experimental stations, or beamlines, around the synchrotron, which they plan to open on 20 June 2016, a date chosen for the symbolism of summer solstice.

The synchrotron that fired up on 25 August is the larger of two that MAX IV is building, with the smaller fourth-generation machine producing electrons of 1.5 GeV for making ‘softer’, or less energetic, X-rays. The combined cost of the machines and of the first eight beamlines will be 4.5 billion Swedish kronor (€450 million), Quitmann says, which is being paid for by the Swedish government. Quitmann says his team reached “a major milestone last night”. But, he adds, “We have still a long way to go.”

Nature doi:10.1038/nature.2015.18253

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/next-generation-x-ray-source-fires-up-1.18253  Original web page at Nature

Categories
News

Non-invasive device could end daily finger pricking for people with diabetes

A new laser sensor that monitors blood glucose levels without penetrating the skin could transform the lives of millions of people living with diabetes. A new laser sensor that monitors blood glucose levels without penetrating the skin could transform the lives of millions of people living with diabetes

Currently, many people with diabetes need to measure their blood glucose levels by pricking their fingers, squeezing drops of blood onto test strips, and processing the results with portable glucometers. The process can be uncomfortable, messy and often has to be repeated several times every day.

The new technology, developed by Professor Gin Jose and a team at the University of Leeds, uses a small device with low-powered lasers to measure blood glucose levels without penetrating the skin. It could give people a simpler, pain-free alternative to finger pricking

The technology has continuous monitoring capabilities making it ideal for development as a wearable device. This could help improve the lives of millions of people by enabling them to constantly monitor their glucose levels without the need for an implant.

It is also good news for healthcare providers as it could provide a simpler and cheaper alternative to both of the current methods — finger pricking, which uses disposable sample strips, or invasive continuous monitors, which use implanted sensors that need regular replacement. Professor Jose said: “Unlike the traditional method, this new non-invasive technology can constantly monitor blood glucose levels.

“As well as being a replacement for finger-prick testing, this technology opens up the potential for people with diabetes to receive continuous readings, meaning they are instantly alerted when intervention is needed. This will allow people to self-regulate and minimise emergency hospital treatment. This wearable device would then be just one step from a product which sends alerts to smart phones or readings directly to doctors, allowing them to profile how a person is managing their diabetes over time.”

The technology is licensed to Glucosense Diagnostics, a spin-out company jointly formed and funded by the University of Leeds and NetScientific plc, a biomedical and healthcare technology group specialising in commercialising transformative technologies from leading universities and research institutes.

Sir Richard Sykes, Chairman of NetScientific, said: “Diabetes is a growing problem, with the need for non-invasive glucose monitoring becoming ever more critical. This unique technology could help empower millions of people to better manage their diabetes and minimise interventions with healthcare providers. The ultimate development of two distinct products — a finger-touch and a wearable — could give people with different types of diabetes the option of a device that best suits their lifestyle.”

At the heart of the new technology is a piece of nano-engineered silica glass with ions that fluoresce in infrared light when a low power laser light hits them. When the glass is in contact with the users’ skin, the extent of fluorescence signal varies in relation to the concentration of glucose in their blood. The device measures the length of time the fluorescence lasts for and uses that to calculate the glucose level in a person’s bloodstream without the need for a needle. This process takes less than 30 seconds.

Professor Jose said: “The glass used in our sensors is hardwearing, acting in a similar way as that used in smartphones. Because of this, our device is more affordable, with lower running costs than the existing self-monitoring systems.

“Currently, we are piloting a bench top version in our clinical investigations but aim to develop two types of devices for the market. One will be a finger-touch device similar to a computer mouse. The other will be a wearable version for continuous monitoring.”

The results of a pilot clinical study, carried out at the Leeds Institute of Cardiovascular and Metabolic Medicine under the supervision of Professor Peter Grant, suggest that the new monitor has the potential to perform as well as conventional technologies. More clinical trials and product optimization are required for regulatory approvals and before the technology can be put on the market.

Professor Grant, Professor of Medicine at the University of Leeds and Consultant diabetes specialist, said: “Non-invasive monitoring will be particularly valuable in young people with Type 1 diabetes. Within this group, those who are attempting very tight control such as young women going through pregnancy or people who are experiencing recurrent hypoglycaemia could find this technology very useful.”

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/07/150714200110.htm  Original web page at Science Daily