Saturday, 8 July 2017

Genetics may lie at the heart of crop yield limitation


Source: Society for Experimental Biology
Summary:
You might think that plants grow according to how much nutrition, water and sunlight they are exposed to, but new research shows that the plant's own genetics may be the real limiting factor.

FULL STORY

Comparison of growth differences in wild-type (left) and growth-repressor mutant (right) Arabidopsis plants.
Credit: Dr Nick Pullen
              You might think that plants grow according to how much nutrition, water and sunlight they are exposed to, but new research by Dr Nick Pullen and a team from the John Innes Centre, UK shows that the plant's own genetics may be the real limiting factor.
"This could have potentially big implications for the agricultural industry," says Dr Pullen, "Our model plant is in the same family as cabbages, so it's easy to imagine creating giant cabbages or growing them to the desired market size faster than at present."
               It was previously assumed that plant growth was generally resource-limited, meaning that plants would only grow as large and fast as they could photosynthesise. However, Dr Pullen and his team present evidence that plant growth is actually "sink-limited," meaning that genetic regulation and cell division rates have a much bigger role in controlling plant growth than previously thought: "We are proposing that plant growth is not physically limited by Net Primary Productivity (NPP) or the environment, but instead is limited genetically in response to these signals to ensure they do not become limiting."
By genetically altering the growth repressors in Arabidopsis, Dr Pullen and his team were able to create mutant strains. They identified the metabolic rates of the different plant strains by measuring rates of photosynthesis and respiration, as well as comparing the size and weight of the plants to monitor differences in physical growth.
             Dr Pullen and the team also grew the mutant plant strains at different temperatures to see if this changed their results: "When grown at different temperatures we still find a difference in size of our plants between wildtype and the mutants. This suggests our results should be applicable in different climates."
The impact of these results is wide-reaching, and Dr Pullen suggests that it may even change how we think about global climate data: "Climate models need to incorporate genetic elements because at present most do not, and their predictions would be much improved with a better understanding of plant carbon demand."

Thursday, 6 July 2017

Utah is home to earliest use of a wild potato in North America


Four Corners potato previously unknown part of ancient human diet

Source: University of Utah
Summary:
Potato starch residues have been discovered in the crevices of a 10,900-year-old stone tool in Escalante, Utah -- the earliest evidence of wild potato use in North America. This is the first archaeological study to identify Solanum jamesii, a wild species native to the southwestern United States, as an important part of ancient human diets. The long history could mean that the species was transported, cultivated or even domesticated.

FULL STORY

             Louderback holds the tiny tubers of S. Jamesii, the Four Corners potato. U researchers discovered the spud's starch residues in the crevices of a 10,900-year-old stone tool in Escalante, Utah -- the earliest evidence of wild potato use in North America.
Credit: University of Utah
               The town of Escalante in southern Utah is no small potatoes when it comes to scientific discovery; a new archaeological finding within its borders may rewrite the story of tuber domestication.
Researchers from the Natural History Museum of Utah and Red Butte Garden at the University of Utah have discovered potato starch residues in the crevices of a 10,900-year-old stone tool in Escalante, Utah -- the earliest evidence of wild potato use in North America. This is the first archaeological study to identify a spud-bearing species native to the southwestern United States, Solanum jamesii, as an important part of ancient human diets. The researchers pieced together evidence from stone tools, ethnographic literature and modern gardeners to show that Utahans have used the species intermittently for over 10,000 years. The Escalante area was even previously known as "Potato Valley" to early settlers.
Several Native American tribes, including Apache, Hopi, Kawaik, Navajo, Southern Paiute, Tewa, Zia and Zuni, consumed S. jamesii. The groups used various cooking and processing techniques, including boiling the potatoes, grinding them into flour or yeast, and mixing the potatoes with clay to reduce bitterness. Some groups still tend their potato populations in cultivated gardens.
The long history could mean that the species was transported, cultivated or even domesticated. If true, S. jamesii would be the first example of a plant domesticated in the western U.S. To find out, the researchers are collaborating with geneticists from the United States Department of Agriculture, who are mining S. jamesii's DNA for genes resistant to drought and disease that could help diversify current potato crops to be more resilient.
            "This potato could be just as important as those we eat today not only in terms of a food plant from the past, but as a potential food source for the future," says Lisbeth Louderback, senior author of the study that published online July 3 in the Proceedings of the National Academy of Sciences. "The potato has become a forgotten part of Escalante's history. Our work is to help rediscover this heritage." Louderback is an assistant professor of anthropology at the U and curator of archeology at the Natural History Museum of Utah.
                                                                                                                                                                     S. tuberosum vs S. jamesii
           The potatoes we buy at the grocery store are all varieties of a single species, Solanum tuberosum, that was domesticated in the South American Andes more than 7,000 years ago. Since then, S. tuberosum has diversified into the reds, russets and thousands of other potato types for sale in markets around the world.
The new study deals with S. jamesii, a wild species found in the shady shelter of oaks, sagebrush and piñon pines across the Four Corners region of the southwestern U.S. The so-called Four Corners potato is most abundant in the highlands of New Mexico, where its green leaves and delicate white flowers are scattered throughout piñon-juniper woodlands. In Utah, however, the plants only grow in sparse, isolated populations near archaeological sites, suggesting that ancient people carried the tubers to the area. Only five small populations of plants are known in the Escalante Valley, including one just 150 meters from the archaeological site, North Creek Shelter. The researchers have enlisted the Escalante community to help conserve the plants and preserve their cultural heritage.
"It's hard to persuade the general public to care about rare plants. But this one has a real history associated with native people, with pioneers, with folks living though the depression and with the residents in Escalante today," says Bruce Pavlik, director of conservation at Red Butte Garden and co-author of the study. "Across the range, it really should be treated as an antiquity, in a sense."
                                                                                                                                                                     Manos and metates: ancient food processors
           Louderback analyzed stone tools from North Creek Shelter in the Escalante Valley, one of Utah's oldest archaeological sites with an 11,000-year history. Its residents were mostly hunters and gatherers until the Fremont and Ancestral Puebloan cultures arrived and began cultivating crops. Today, the Southern Paiute inhabit this region along with descendants of Mormon settlers.
Archaeologists use mathematical models derived from foraging theory to describe how and why people foraged for food resources. Using what is called the diet breadth model, archaeologists rank dietary animals and plants according to their energy content and the effort required to harvest and process the food. The discovery of S. jamesii consumption adds a new energy source that has been largely ignored in ancient diets, partly because tubers don't preserve well in archaeological deposits. Unlike animal bones and corn cobs, tubers are composed of soft tissues that disintegrate easily. Yet they pack a caloric punch, and are important for understanding ancient peoples' way of life.
            Louderback examined large sandstone slabs called metates and handheld grinding stones called manos, the ancient food processors on which people prepared meals. She found microscopic starch granules that previous archaeologists never suspected were present.
"Grinding plant tissues with manos and metates releases granules that get lodged in the tiny cracks of stone, preserving them for thousands of years. Archaeologists can retrieve them using chemicals, modern microscopy and advanced imaging techniques," says Louderback.
All starch granules have concentric circles that grow outward like tree rings. The origin of growth begins with what's called the hilum. The majority of plant species have starch granules with hila at the center of the grain. However, the hila of granules filling Louderback's microscope slides were off-center. Only a few species from the Four Corners region produce starch granules with that specific characteristic; S. jamesii is one of them.
               She and NHMU postdoctoral research associate Nicole Herzog, now a lecturer at Boise State University, analyzed granules from modern-day S. jamesii to establish a set of five characteristics that accurately identified the wild potato, starting with the off-center hilum. Starch granules with five out of five characteristics were a verified wild potato. They analyzed tubers from three different modern populations, 100 granules per tuber.
Louderback and Pavlik checked for the characteristics on granules found on the ancient stone tools from North Creek Shelter. Out of the 323 total starch granules, 122 had the off-center hilum. Of those, nine were verified S. jamesii and another 61 were either likely or possibly S. jamesii.
                                                                                                                                                                           The future of the Four Corners potato
                The researchers are collaborating with colleagues from the USDA Potato Genebank, who have studied the genetics of S. jamesii since the 1990s. Future efforts will focus on understanding patterns of genetic diversity across the Four Corners region to look for clues about whether it was transported, manipulated or even domesticated.
The researchers want to make the potatoes available for the Escalante community to grow in their gardens to help with conservation. But first, they need to untangle the mysterious ecology of the potato in the wild -- its pollinators and conditions necessary for sexual reproduction are still unknown.
"We are working with the people of Escalante to bring awareness to this valuable resource and show them what the species looks like, where it grows, its tremendous history and enlist their help as stewards of the Four Corners potato," says Pavlik.

Global use of wastewater to irrigate agriculture at least 50 percent greater than thought


With 885 million consumers exposed to health risks, study calls for urgent investments in improved sanitation

Source: IOP Publishing
Summary:
The use of untreated wastewater from cities to irrigate crops downstream is 50 percent more widespread than previously thought, according to a new study.

FULL STORY

Aerial view of sewage water treatment plant. (Stock image)
Credit: © josefkubes / Fotolia
           The use of untreated wastewater from cities to irrigate crops downstream is 50 percent more widespread than previously thought, according to a new study published this week in the journal Environmental Research Letters.
            The study relies on advanced modeling methods to provide the first truly comprehensive estimate of the global extent to which farmers use urban wastewater on irrigated cropland. Researchers analyzed data with geographic information systems (GIS) rather than depending on case study results, as in previous studies.
           The researchers also assessed for the first time 'indirect reuse', which occurs when wastewater gets diluted but still remains a dominant component of surface water flows. Such situations account for the majority of agricultural water reuse worldwide, but have been difficult to quantify on a global level due to different views of what constitutes diluted wastewater versus polluted water.
Considering consumer safety the foremost priority, study authors highlight the need to mitigate public health risks through measures taken along the entire food supply chain. This includes improved wastewater treatment, but also preventive steps on farms and in food handling, since capacity for water treatment is increasing only slowly in developing countries.
          According to the study, farmers' use of wastewater is most prevalent in regions where there is significant wastewater generation and water pollution. In these circumstances, and where safer water is in short supply, wastewater offers a consistent and reliable means of irrigating fields, including high-value crops, such as vegetables, which often require more water than staple foods. Where raw wastewater is available, farmers may tend to prefer it because of its high concentrations of nutrients, which can lessen the need to apply purchased fertilizers. In most cases, however, farmers' use of this water is motivated by basic needs; they simply do not have alternatives.
             "The de facto reuse of urban wastewater is understandable, given the combination of increasing water pollution and declining freshwater availability, as seen in many developing countries," said Anne Thebo, a recent graduate at the University of California, Berkeley in the USA and lead author of the study. "As long as investment in wastewater treatment lags far behind population growth, large numbers of consumers eating raw produce will face heightened threats to food safety."
           Results show that 65 percent of all irrigated areas are within 40 km downstream of urban centers and are affected by wastewater flows to a large degree. Of the total area of 35.9 million hectares, 29.3 million hectares are in countries with very limited wastewater treatment, exposing 885 million urban consumers as well as farmers and food vendors to serious health risks. Five countries -- China, India, Pakistan, Mexico and Iran account for most of this cropland. These new findings supersede a widely cited 2004 estimate, based on case studies in some 70 countries and expert opinion, which had put the cropland area irrigated with wastewater at a maximum of 20 million hectares.
"Gaining a better grasp of where, why and to what extent farmers use wastewater for irrigation is an important step toward addressing the problem," said second author Pay Drechsel of the International Water Management Institute (IWMI), who leads the CGIAR Research Program on Water, Land and Ecosystems. "While actions aimed at protecting human health are the first priority, we can also limit the hazards through a variety of tested approaches aimed at safely recovering and reusing valuable resources from wastewater. These include the water itself but also energy, organic matter and nutrients, all of which agriculture needs. Through such approaches, we have been helping the World Health Organisation (WHO) respond to the wastewater challenge over the years."
              "We hope this new study will focus the attention of policy makers and sanitation experts on the need to fulfill Sustainable Development Goal 6, particularly target 3, which calls for halving the proportion of untreated wastewater, and increasing recycling and safe water reuse," added Drechsel.
"One major challenges is to cultivate behavior change from farm to fork, especially where risk awareness is low. Another consists of larger scale efforts to put the recovery and reuse of resources from wastewater and other waste on a business footing to make its management more attractive for the public and private sectors. Safe resource recovery and reuse have significant potential to address the health and environmental risks, while at the same time making cities more resilient and agriculture more sustainable, contributing to more circular economies."

Research shows How cats and cows protect farm children from asthma


Source: University of Zurich
Summary:
It is a known fact that microbes on farms protect children from asthma and allergies. But even non-microbial molecules can have a protective effect. Immunologists have shown that a sialic acid found in farm animals is effective against inflammation of lung tissue. This study opens up a wide variety of perspectives for the prevention of allergies.

FULL STORY

Milking cow (stock image).
Credit: © Ror / Fotolia
             It is a known fact that microbes on farms protect children from asthma and allergies. But even non-microbial molecules can have a protective effect: Immunologists from the University of Zurich have shown that a sialic acid found in farm animals is effective against inflammation of lung tissue. This study opens up a wide variety of perspectives for the prevention of allergies.
More and more people suffer from allergies and asthma. In the past decades, these diseases have massively increased in industrialized countries. Today, about 30 percent of children have allergies with the exception of farm children. Among farm children, the disease is increasing less dramatically than in the case of their friends who live in the same village, but not on a farm. Microbes that occur in higher amounts and greater diversity on farms protect farm children from allergies and asthma. An environment that is not highly hygienic has a positive effect on the development of the immune system as it learns not to react to harmless materials as is the case with allergies.
                                                                                                                                                                    A sialic acid acts as protection
           Not only microbes protect against asthma evidently, but also farm animals: Petting cats and cows and drinking farm milk can also prevent asthma, as the team of researchers headed up by Remo Frei of the Swiss Institute of Allergy and Asthma Research from the University of Zurich in cooperation with the Center for Allergy Research and Education (CK-CARE) in Davos and the Children's Hospital of Eastern Switzerland in St. Gallen: "Early childhood contact with animals and the consumption of food of animal origin seems to regulate the inflammatory reactions of the immune system," says immunologist Frei. His study shows that a non-microbial substance, a sialic acid, is responsible for this mechanism. This substance is wide spread in vertebrates -- and therefore in many farm animals but missing in the human organism: N-Glycolylneuraminic acid (Neu5Gc).
                                                                                                                                                                 Antibodies as measure for contact with farm animals
             Based on a genetic mutation, humans do not produce Neu5Gc. They can absorb sialic acid through contact with animals or by eating food of animal origin and integrate it into their glycoproteins. Contact with Neu5Gc triggers an antibody reaction in humans which can act as a measure for contact with Neu5Gc, that is, with farm animals. The researchers led by Remo Frei have measured the concentrations of Neu5Gc antibodies in the serum samples of children collected within the scope of two epidemiological studies financed by the European Union (PARSIFAL and PASTURE study).
                                                                                                                                                                      Data comparison of more than a thousand children
            As a comparison of the Neu5Gc antibody concentration of over a thousand children and the occurrence of asthma has clearly shown, "Farm children have many more antibodies against Neu5Gc in their blood and children with more antibodies suffered considerably less from asthma," Frei says. The positive effect of sialic acid Neu5Gc on the respiratory system was confirmed using a mouse-model: The Neu5Gc molecules consumed with food improved the pulmonary function of the mice, therefore reducing asthma symptoms.
                                                                                                                                                                           From farm effect to allergy prevention
             To understand the mechanism of how Neu5Gc affects the human immune system, researchers analyzed various cells of the immune system that play a role during an inflammatory reaction. With an interesting result  both in the children tested and on the animal model: Contact with Neu5Gc did not reduce immunoglobulin E, the antibody that frequently occurs during allergic reactions, but it initiates an anti-inflammatory reaction of the immune system. "This takes place through so-called regulatory T-cells, which have an increased presence," Frei explains. "These T-cells dampen incorrect responses of the immune system and have a strong anti-inflammatory effect. Our research results open up opportunities for transferring the protective effect of farms to all children. In this way, we can possibly lay an important foundation stone for effective allergy prevention."

Saturday, 1 July 2017

According to Research, Food allergies linked to childhood anxiety


Source: Columbia University's Mailman School of Public Health
Summary:
Researchers studied the link between food allergy and childhood anxiety and depression among a sample of predominantly low socioeconomic status minority children and found that children with a food allergy had a significantly higher prevalence of childhood anxiety. Food allergies were not associated with symptoms of childhood depression or with symptoms of anxiety or depression among their caregivers.

FULL STORY

Children with a food allergy had a significantly higher prevalence of childhood anxiety, a new study has found.
Credit: © vejaa / Fotolia
                 Researchers at Columbia University's Mailman School of Public Health and Ferkauf Graduate School of Psychology and Albert Einstein College of Medicine studied the link between food allergy and childhood anxiety and depression among a sample of predominantly low socioeconomic status minority children. The results showed that children with a food allergy had a significantly higher prevalence of childhood anxiety. Food allergies were not associated with symptoms of childhood depression or with symptoms of anxiety or depression among their caregivers. The results are published in the Journal of Pediatrics.
                 Food allergies are increasingly common among youth in the U.S. with recent estimates as high as 8 percent. Until now little was known about the prevalence of food allergy in low socioeconomic ethnic minority populations.
The researchers studied 80 pediatric patients ages 4-12 years, 8 years old on average, with and without food allergy and their caregivers from urban pediatric outpatient clinics in the Bronx, New York. They controlled for an asthma diagnosis in the children, as anxiety and mood disorders are more prevalent among youth with asthma and especially more common in low socioeconomic minority children.
Among the children with a food allergy, 57 percent reported having symptoms of anxiety compared to 48 percent of children without a food allergy. Approximately 48 percent of the children had symptoms of depression with or without a food allergy.
                 "Management of food allergy can be expensive both in terms of food shopping, meal preparation, and the cost of epinephrine auto-injectors, which expire annually," said Renee Goodwin, PhD, in the Department of Epidemiology at the Mailman School of Public Health and lead author. "These demands could result in higher levels of anxiety for those with fewer financial resources and further heighten anxiety symptoms in children and their caregivers."
The results suggest that food allergy is particularly linked to elevated social anxiety and fear of social rejection and humiliation. "There are a number of possible explanations for the relationship found between food allergy diagnosis and increased social anxiety issues in this sample of pediatric patients," noted Dr. Goodwin. "Management of a potentially life-threatening condition may be anxiety provoking, and some children may experience increased social anxiety about being "different" from other children depending on their age and how food allergy is managed by adults in a particular setting."
                 The researchers also point out a possible explanation for not finding a link between food allergy and depression in children. The sample was young, and the mean age of onset for depression is significantly later than anxiety. "It would be worthwhile to examine these relationships among older adolescents and young adults with food allergy who are at the peak of risk for depression onset, especially because early anxiety is associated with increased risk for subsequent onset of depression," said Jonathan Feldman, PhD, professor of Psychology at Ferkauf Graduate School of Psychology, Yeshiva University.
"With the high prevalence of food allergies today, education in schools remains a priority," said Dr. Goodwin. "Given the strong association between food allergy and social anxiety in children future investigations on the food allergy-mental health relationship are also warranted in clinical, school, and community-based settings which could aid in the development of interventions."

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Miniature technology, big hope for disease detection


Smple printing method to create effective disease detection tools

Source: Okinawa Institute of Science and Technology (OIST) Graduate University
Summary:
Researchers develop a simple printing method to create effective disease detection tools.

FULL STORY

             First, a flexible stamp is inked with the APTES solution (i). The stamp is then pressed onto the glass surface (ii). A microfluidic channel is placed over the APTES pattern on the glass (iii), and the device is ready to be used to immobilize bioreceptors and, eventually, to help make a diagnosis (iv).
Credit: Okinawa Institute of Science and Technology Graduate University (OIST)
The field of medicine is always on the lookout for better disease diagnostic tools -- simpler, faster, and cheaper technologies to enhance patient treatment and outcomes. Currently, microfluidic bioassay devices are the preferred diagnostic tools that allow clinicians to measure the concentration of disease biomarkers within a patient's biological sample, such as blood. They can indicate the likelihood of a disease based on a comparison of the biomarker concentration in the sample relative to the normal level. To detect this concentration, the patient's sample is passed across a surface containing immobilized bioreceptors, or "biomarker-capturing" molecules that have been attached to this surface. A researcher can then record the biomarker abundance, determine whether the level is normal, and reach a diagnosis. Since the efficiency of these devices relies on how intact and functional the attached bioreceptors are, immobilizing these bioreceptors without causing damage has proved daunting.
            Over the last two decades, microcontact printing, which uses a rubber stamp to immobilize the bioreceptors, has been established as a robust method to create a variety of assays with multiple applications. Yet this method also has its flaws, particularly when utilized at the nano scale -- the scale where proteins and DNA reign. At this scale, the harsh and elaborate techniques currently used compromise the device's resolution, whether by deforming the stamp or damaging the bioreceptors, thus yielding data somewhat unmanageable for use in diagnostics or other applications. However, in a recent article published in the journal Analyst, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) describe a new sequence of printing steps that have rectified these issues.
For microcontact printing, "you need a stamp, an ink, and a surface, and then you create your pattern on your surface. It's as simple as that," explains Shivani Sathish, OIST PhD student in the Micro/Bio/Nanofluidics Unit, and first author on the paper.
               The stamp is made of polydimethylsiloxane, which is a flexible solid similar to the rubber used in everyday stamps. The ink is a solution composed of silicon- and oxide-containing molecules called APTES, and the surface is glass. After coating the stamp with the ink, the stamp is pressed onto the glass, and then removed after a short incubation. The result is a patterned layer of APTES on the glass -- a checkerboard of regions with or without APTES. Next, a microfluidic device, which contains one or more microchannels configured to guide fluid through specified pathways, is sealed over the patterned glass. Finally, the bioreceptors are chemically linked to the APTES regions within the microfluidic channels. The device as a whole is about the size of a postage stamp.
               The system is now ready for use as a diagnostic assay. To carry out the assay, a fluid sample from a patient is delivered through the microfluidic device attached to the glass. If the pertinent disease biomarker is present, the molecule will "stick" to the areas containing the bioreceptors.
What is important about the APTES solution is its convenient chemistry. "Depending on your bioreceptor of interest, you just have to choose the appropriate chemistry to link the molecule with the APTES," Ms. Sathish explains. Or in other words, one stamp can be used to prepare an assay with the ability to immobilize a variety of different bioreceptors one stamp allows for multiple tests and diagnoses on a single surface.         This feature would be advantageous for diagnosing complex diseases such as cancer, which relies on tests that can detect multiple markers to improve the diagnosis.
                In their research, Ms. Sathish and colleagues developed an improved technique to create the most optimal disease diagnostic device for use at the nano scale. Here, they first patterned nanoscale features of APTES using an ink made of APTES in water, as opposed to harsh chemicals, which eliminated the stamp-swelling issue. Then, they immobilized the bioreceptors onto the surface as the very last step of the process, after patterning the APTES and attaching the microfluidic device. By attaching the bioreceptors as the final step, the researchers avoided exposing them to extreme and damaging conditions. They then demonstrated the efficacy of the final device by running an assay to capture the biomarkers interleukin 6 and human c-reactive protein, two substances that are often elevated in the body during inflammation.
                "The final goal is to create a point-of-care device," explains OIST Professor Amy Shen, who headed the research.
"If you get your bioreceptors pre-immobilized within microfluidic devices you can then use them as diagnostic tools as and when required," Ms. Sathish continues. "[Eventually] instead of having a whole clinical team that processes your sample...we're hoping that the patients can do it themselves at home."

Find out How the liver unclogs itself


Findings could potentially improve prognosis of infants with rare liver disease

Source: National University of Singapore
Summary:
Scientists have described the mechanical principles adopted by liver cells as they remove excess bile during obstructive cholestasis.

FULL STORY

              This is a schematic diagram illustrating how hepatocytes or liver cells clear excess bile from blocked ducts. (A) Bile ducts are blocked in diseases such as biliary atresia. (B) Bile builds up behind the blockage, putting pressure on the surrounding cells that make up the walls of the duct. (C) If the pressure increases, the actin cortex, which lies inside the cell, may rupture. Once the actin filament network is fragmented, the bile will push the cell membrane into the cell, through the disrupted actin network. (D) If the actin network cannot be repaired, then the membrane will continue to be pushed inside until it breaks off into bubble-like vesicles. These vesicles carry the bile through the cell and away from the blockage.
Credit: Mechanobiology Institute, Singapore
               A multi-disciplinary team of researchers from the Mechanobiology Institute, Singapore (MBI) at the National University of Singapore (NUS), the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR, and BioSyM, Singapore-MIT Alliance for Research and Technology have described the mechanical principles adopted by liver cells as they remove excess bile during obstructive cholestasis. This study was published online in the Journal of Hepatology earlier this year.
The research team comprises team leader Professor Hanry Yu, who is a Principal Investigator at MBI and IBN; Mr Kapish Gupta, who is a graduate student at MBI and first author of the paper; as well as their fellow MBI researchers -- Associate Professor Virgile Viasnoff, Associate Professor Low Boon Chuan, and Assistant Professor Pakorn (Tony) Kanchanawong.
                                                                                                                                                                        New mechanism discovered in the liver's response to blocked bile ducts
               Biliary atresia is a rare, life-threatening liver disease that affects infants, and in particular, babies of Asian and African American descent. Although the cause of the disease remains unclear, the first symptoms are usually detected within weeks of birth.
Dubbed the 'chemical factory' of our body, the liver performs over 500 biological functions. Foremost among them is the synthesis and storage of essential biochemical substances, as well as the elimination or neutralisation of harmful toxins from the blood.
                 One of the most important functions of the liver is the production of bile, which is responsible for the organ's detoxifying effects. Bile flows through a network of tubes known as the biliary tract, into the small intestine. During its passage the bile digests fats, and absorbs essential fatty acids. It also facilitates the elimination of waste products via the faeces.
In babies suffering from biliary atresia, bile accumulates in the biliary ducts. This means that liver function is ultimately impeded and without surgical intervention, long-term liver damage or cirrhosis will occur.
To date there are no drugs available to treat biliary atresia. However, there is renewed hope that this may one day change, with recent findings from research conducted at MBI revealing how liver cells already possess the ability to eliminate excess bile from tubes located inside the liver, which feed bile into the biliary ducts.
                                                                                                                                                                              How liver cells eliminate bile from blocked ducts
               The key to the liver's ability to eliminate excess bile is the fact that the 'tubes' through which bile enters the biliary tract are not merely a set of inactive pipes, but are actually hollow spaces between living cells. The walls of the tubes are essentially the outside surfaces of the cells.
To investigate how the liver responds to bile accumulation, the research team used an artificial culture system, which allowed the easy manipulation of cultured liver cells. They then used high-end imaging techniques to visualise the dynamics of the tubes that develop within this culture system.
The team sought to investigate the response of the cells that line a blocked bile duct by obstructing the bile tract artificially and observing what happened. What they found was that as the bile accumulated behind the blockage, the tube began to swell or bulge, and this put pressure on the cells that make up the wall of the tube.
              The key to the removal of excess bile lies in the internal structure of the cell itself. Immediately adjacent to the cell membrane is a network of protein cables or filaments known as the actin cortex. This structure serves to strengthen the cell, and help it retain its shape and integrity even when external forces are applied to the cell surface external forces like the increased pressure from a build-up of fluid. Normally the actin cortex is able to counter the forces applied to it, and even when some damage to the network is incurred, it is quickly fixed by proteins that can reassemble the actin filaments.
However, when the pressure becomes too great, the actin cortex will rupture, and it will not be repaired. Although the bile cannot simply pass through the membrane, it can, as the researchers discovered, push the membrane into the cell, through the gap in the ruptured actin cortex. As this occurs a bubble-like vesicle forms inside the cell, and it is inside this vesicle that the bile enters and passes through the cell. The bile is essentially packaged inside these vesicles for its transport through the cell, and away from the site where it had accumulated.
               Although the liver does not stop producing bile even when the biliary ducts are blocked, it is now evident that the liver does have a process in place to look after itself when a potentially damaging amount of bile builds up inside a blocked duct.
It is hoped that this mechanism may one day be therapeutically targeted to improve the prognosis for infants with biliary atresia. As the researchers showed, the rate of vesicle formation, and hence the uptake of excess bile into liver cells, can indeed be adjusted using drugs, at least in the cell culture setting. Improving the effectiveness of this naturally occurring mechanism, by increasing, for example, the rate of vesicle formation, may indeed encourage bile elimination from the blocked duct so as to avoid long-term liver damage and increase the effectiveness of surgical intervention.

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