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  • Affordable and mobile purification of dialysis water
    952    

    NEWS

       |   11/10/2019    
    Affordable and mobile purification of dialysis water
    Medical & Healthcare  Health care equipment

    People who suffer from end stage renal desease frequently undergo dialysis on a fixed schedule. For patients this artificial washing of the blood is a major burden. To remove toxins from the blood, large quantities of dialysis water for clearance are required. Until now there has been no solution so far to recover this dialysate cost-effectively. Therefore a cryo-purification method is being developed by Fraunhofer researchers that clears the water without loosing it. This approach not only reduces costs – it may even pave the way for a wearable artificial kidney by milder long-term dialysis treatment at complete water autonomy. Some 90,000 people in Germany every year have to undergo dialysis three times a week for four to five hours, because their kidneys no longer function properly and cannot eliminate toxins sufficiently. During treatment harmful metabolites are removed from the blood by transferring them outside the body via a semipermeable membrane into a dedicated dialysis fluid called the dialysate. The pores of the membrane are so narrow that only toxins up to a certain size can pass them. Small molecules such as water, electrolytes and uremic toxins – urea, uric acid and creatinine – transit the membrane into the cleaning fluid, while large molecules such as proteins and blood cells are rejected. The entire blood is recirculated and cleared approximately three times per hour. Dialysate can only be used once For a dialysis treatment, approx. 400 liters of dialysate are required. Hospitals and dialysis centers prepare this water using reverse osmosis systems, which consume a lot of energy and are expensive. It is challenging that dialysate can only be utilized once, as it disappears as waste water after the blood purification treatment. To treat 90,000 patients per year this requires more than 5.6 million cubic meters of ultrapure water. In many regions of the world this requirement is not met. According to estimates, over a million people die every year by lacking access to dialysis. “Dialysis water is precious. Germany’s one year dialysis water fills a 175m cube. Up to now there has been no cost-effective method to reclaim dialysate,” says Dr. Rainer Goldau, scientist at the Department of Extracorporeal Immunomodulation at the Fraunhofer Institute for Cell Therapy and Immunology IZI in Rostock, whose research work is focused upon this subject. The body approximately produces 25 grams of urea every day. This molecule – being of nearly the waters molecular size – also passes the filter membrane into the dialysate. The reverse osmosis technique, employed to generate potable water, does not have a sufficient rejection rate for urea, rendering it unsuitable for dialysis water recovery. Although there are elaborate enzymatic techniques capable of clearing dialysate such that it can be reused on patients, the filters and cartridge required for them are very expensive. Regions of significant indigence in combination with water scarceness cannot afford such techniques. Dialysis with patient’s intrinsic water Dr. Goldau is therefore investigating another variant called cryo-purification, which is based on freeze concentration known from beverage industries. The aim is to reclaim more than 90% of the water extracted from patients using this method. The idea is to upconcentrate toxins to only those two or three liters of water per day that are to be eliminated anyway during every dialysis. Patients can refill this water by drinking. The remainder – generally 25 to 30 liters per day – is cleared and fed back to dialysis. “In our experiments the volume of water that has to be discarded is less than 10 percent. This amount is required to filter the toxins. Thus, when it comes to upconcentration our technique is almost as effective as the kidneys themselves,” says Goldau. In this way, the researcher and his team want to establish an adequate dialysis that uses the patient’s own water resources without dehydration. Expensive filters and cartridges would no longer be required. But how does the cryo-purification work? It takes advantage of the ice crystals capability to exclude all previously dissolved contaminations. They are repelled to the surface of the crystal. “The ice crystals formed when water freezes have the ability to simultaneously expel impurities. This permits to separate all the uremic toxins – i.e. metabolic waste products that the body needs to eliminate via the urine,” explains Goldau. This procedure can be implemented within washcolumns that are customary at beverage or chemical industries. For mobile dialysis, a small wash column is sufficient to produce 30 to 40 ml/min of dialysate. To prepare fresh dialysate, only a small amount of energy is required. The electricity could arbitrarily be drawn from mains, a car battery or solar panels. A respective lab demonstrator with a chiller is being constructed and a patent application has been filed for the process. The researchers are currently working on an automated solution, for the development of which they still need support from industrial partners. Wearable kidney for home dialysis “Our form of dialysis can even be designed to be mobile – wearable hemodialysis would be feasible.” In the vision of the Rostock-based researcher the patient is provided with a vascular access via which the blood and the excess water are extracted and returned. This is connected to a vest with a dialysis filter membrane, which contains disposable water chambers of up to 4 liters of volume. Every two or three hours the patient connects the vest to a non-stationary base unit, which flushes the waste dialysate and refills fresh water, both within the same period it takes a healthy individual to visit the toilet. Current dialysis in hospitals puts a huge strain on the body and greatly affects the quality of the patients life. According to studies, only between 20 and 40 percent of patients are still alive after ten years. With long-term dialysis that is tap-water independent and can be performed anytime at home or at work, the morbidity rate and the costs of dialysis could be reduced. In addition it would be available to people within the drought belts worldwide as well. Another advantage is that dialysis centers and hospitals could reduce their water costs. Goldau estimates that his process could save 90 percent of the water – and thus also the waste water – used for dialysis, as it is in a reclamation cycle. “Most of the water is recycled.” The physicist expects that the system can be market-ready within around five to seven years from the start of development.

  • Biosensor: detecting patient's antibiotic levels with micron…
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    NEWS

       |   04/10/2019    
    Biosensor: detecting patient's antibiotic levels with micron…
    Medical & Healthcare  Medical Test Services

    Small, non-invasive patches worn on the skin can accurately detect the levels of medication in a patient's system, matching the accuracy of current clinical methods. In a small-scale clinical evaluation, researchers at Imperial College London have shown for the first time how microneedle biosensors can be used to monitor the changing concentration of antibiotics. Their findings, published today in The Lancet Digital Health, show the sensors enable real-time monitoring of changes in antibiotic concentration in the body, with similar results to those obtained from blood tests. The team believes the technology could change how patients with serious infections are treated by showing how quickly their bodies 'use up' medications they are given. The researchers add that if future development and testing proves successful and the technology reaches the clinic, it could help to cut costs for the NHS, reduce drug-resistant infections and improve treatment for patients with life-threatening infections and improve the management of less serious ones. They add that biosensors could reduce the need for blood sampling and analysis as well as offer more efficient, personalized drug delivery that could potentially be delivered outside of the hospital setting for outpatients. Dr Timothy Rawson, from Imperial's Department of Infectious Disease and who led the research, said: "Microneedle biosensors hold a great potential for monitoring and treating the sickest of patients. When patients in hospital are treated for severe bacterial infections the only way we have of seeing whether antibiotics we give them are working is to wait and see how they respond, and to take frequent blood samples to analyze levels of the drugs in their system – but this can take time." "Our biosensors could help to change that. By using a simple patch on the skin of the arm, or potentially at the site of infection, it could tell us how much of a drug is being used by the body and provide us with vital medical information, in real time." Microneedle biosensors use a series of microscopic 'teeth' to penetrate the skin and detect changes in the fluid between cells. These teeth act as electrodes to detect changes in pH and can be coated with enzymes which react with a drug of choice, altering the local pH of the surrounding tissue if the drug is present. The technology has been used for continuous monitoring of blood sugar, but the Imperial group has, for the first time, shown its potential for use in monitoring changes to drug concentrations. Professor Alison Holmes, from Imperial's Department of Infectious Disease and director of the NIHR Health Protection Research Unit in HCAI and AMR at Imperial and the CAMO, said: "Technological solutions such as our microneedle biosensor could prove crucial in improving how we use and protect the arsenal of life-saving antibiotics we have available to treat patients. Ultimately, these types of collaborative, multidisciplinary solutions could lead to earlier detection and better treatment of infections, helping to save more lives and protect these invaluable medicines for generations to come."

  • 3D printing: new technique for biomaterials
    1496    

    NEWS

       |   04/10/2019    
    3D printing: new technique for biomaterials
    Medical & Healthcare  Operating equipment

    A new way of 3D printing soft materials such as gels and collagens offers a major step forward in the manufacture of artificial medical implants. Developed by researchers at the University of Birmingham, the technique could be used to print soft biomaterials that could be used to repair defects in the body. Printing soft materials using additive manufacturing has been a big challenge for scientists because if they are not supported, they sag and lose their shape. The technique, called Suspended Layer Additive Manufacturing, uses a polymer-based hydrogel in which the particles have been manipulated to create a self-healing gel. Liquids or gels can be injected directly into this medium and built up in layers to create a 3D shape. The method offers an alternative to existing techniques which use gels that have been minced to form a slurry bath into which the printed material is injected. Called Freeform Reversible Embedding of Suspended Hydrogels (FRESH), these offer many advantages, but frictions within the gel medium can distort the printing. In a study published in Advanced Functional Materials, a team led by Professor Liam Grover, in the School of Chemical Engineering, show how particles in the gel they have developed can be sheared, or twisted so they separate, but still retain some connection between them. This interaction creates the self-healing effect, enabling the gel to support the printed material so objects can be built with precise detail, without leaking or sagging. "The hydrogel we have designed has some really intriguing properties that allow us to print soft materials in really fine detail," explains Professor Grover. "It has huge potential for making replacement biomaterials such as heart valves or blood vessels, or for producing biocompatible plugs, that can be used to treat bone and cartilage damage." SLAM can also be used to create objects made from two or more different materials so could be used to make even more complex soft tissue types, or drug delivery devices, where different rates of release are required.

  • Shedding light on the reaction mechanism of PUVA light thera…
    2618    

    NEWS

       |   23/08/2019    
    Shedding light on the reaction mechanism of PUVA light thera…
    Medical & Healthcare  Operating equipment

    The term 'PUVA' stands for 'psoralen' and 'UV-A radiation'. Psoralens are natural plant-based compounds that can be extracted from umbelliferous plants such as giant hogweeds. Plant extracts containing psoralens were already used in Ancient Egypt for the treatment of skin diseases. Modern medical use began in the 1950s. From then on, they were applied for light-dependent treatment of skin diseases such as psoriasis and vitiligo. From the 1970s onwards, PUVA therapy was used to treat a type of skin cancer known as cutaneous T-cell lymphoma. Psoralens insert between the crucial building blocks (bases) of DNA, the hereditary molecule. When subjected to UV radiation, they bind to thymine -- a specific DNA base -- and thus cause irreversible damage to the hereditary molecule. This in turn triggers programmed cell death, ultimately destroying the diseased cell. Researchers working with Prof. Dr. Peter Gilch from HHU's Institute of Physical Chemistry have now collaborated with Prof. Dr. Wolfgang Zinth's work group from LMU Munich to analyse the precise mechanism of this binding reaction. They used time-resolved laser spectroscopy for this purpose. They found that -- after the psoralen molecule has absorbed UV light -- the reaction takes place in two stages. First, a single bond between the psoralen molecule and thymine forms. A second bond formation then yields a four-membered ring (cyclobutane) permanently connecting the two moieties. The researchers in Düsseldorf and Munich were also able to demonstrate that the first stage takes place within a microsecond, while the second needs around 50 microseconds. They compared this process with the damaging of the 'naked' DNA by UV light. That process also frequently results in cyclobutane rings, but the process takes place considerably faster than when psoralens are present. Prof. Gilch explains the background to the research: "If we can understand how the reactions take place in detail, we can change the psoralens chemically in a targeted way to make PUVA therapy even more effective." Together with his colleague in organic chemistry, Prof. Dr. Thomas Müller, he wants to develop these high-performance psoralen molecules at HHU within the scope of a DFG project.

  • Hope for better cancer treatment in scientific 'blind spot'
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    NEWS

       |   22/08/2019    
    Hope for better cancer treatment in scientific 'blind spot'
    Medical & Healthcare  Clinical Trial, Bioanalytical & Other Pharmaceutical Services

    Damaged DNA inside cells can lead to the development of cancer, neurodegenerative disorders and many other diseases. To fix the problem, organisms have evolved to rapidly tag a number of ‘repair proteins’ near the site of damage with chemical flags. This process, known as ADP-ribosylation (ADPr), acts like an alarm system to identify the place where help is needed. So fundamental is ADPr to understanding how cells deal with DNA damage that some chemotherapy drugs, which have been designed to prevent key enzymes involved in the process from working, are already being used to treat certain types of breast, ovarian and prostate cancers. Yet the underlying molecular mechanisms of ADPr are still poorly understood – something that is limiting our ability to develop new, more effective treatments. It was already known that ADPr flags attach to particular sites on proteins within damaged cells, but it was unclear exactly where. More recent studies have shown that ADPr flags attach to a number of amino acids – the building blocks of proteins. The original aim of the EU-funded INVIVO_DDR_ADPR project was to map all the amino acid sites for ADPr flags in the worm Caenorhabditis elegans – an undertaking that promised to fully reveal the molecular mechanisms for repairing damaged DNA. But after the first set of experiments, the researchers discovered that ADPr flags can also attach to the amino acid serine. Overlooked for 50 years, this is an incredibly important aspect of the DNA repair process; if scientists can understand the regulatory networks that underlie this complex biological process, it will provide new insights for improved treatment of diseases that relate to DNA damage, including cancer. ‘It may seem like a small detail, but in the cell “factory” this is an important mechanism,’ says researcher Juan José Bonfiglio, from the INVIVO_DDR_ADPR research group co-ordinated by Ivan Matic at the Max Planck Institute for Biology of Ageing in Germany. ‘It’s like discovering a new letter in an alphabet you thought you knew – namely the alphabet the cell uses for sending vital internal messages.’ Improving DNA repair to treat disease? Because this finding was so unexpected, the team altered some of the project’s specific aims to focus on this new discovery. They went on to work out the molecular mechanism by which the ADPr signal is ‘written’ on to the amino acid serine and how it is then erased again. Their work has also shown that the flagging of serine plays a very important role in the cell’s response to DNA damage. The team’s work has the potential to provide important insights for the improved treatment of diseases such as cancer, by opening up new possibilities to improve and increase the efficiency of the DNA repair machinery. New tools for science ‘Our discovery revealed how important discoveries may be hidden in scientific “blind spots”,’ says Bonfiglio, who received funding through the EU’s Marie Skłodowska-Curie fellowship programme for this project. The need to progress their research also forced the team to come up with novel tools, which have led to two patent applications. These include a new, first-instance approach to generating antibodies that are site-specific and enable detection of specific ADPr sites. ‘We’re convinced that these tools will be useful not only for our own projects but for the scientific community in general,’ says Bonfiglio.

  • BIOMARKERS INDICATE HEALTH IN OLD AGE
    2329    

    NEWS

       |   22/08/2019    
    BIOMARKERS INDICATE HEALTH IN OLD AGE
    Medical & Healthcare  Clinical Trial, Bioanalytical & Other Pharmaceutical Services

    Researchers can determine the disease vulnerability of older people using a defined set of substances in the blood Researchers on ageing from the Max Planck Institute for Biology of Ageing and the Leiden University Medical Center (LUMC) collaborate to link basic insights from model organisms to the causes of ageing in humans. They found a combination of biomarkers in the blood which could help estimate the disease vulnerability of elderly people in clinical studies and could possibly be used in intervention studies in model organisms that slow down ageing. When basic researchers investigate the molecular basis of ageing, they usually study model organisms such as worms, fruit flies or mice. The Max Planck Institute for Biology of Ageing aims to link basic insights into ageing to the causes and processes underlying ageing-associated diseases in humans and has therefore recruited Prof. Eline Slagboom from the Leiden University Medical Center in the Netherlands (LUMC) as a Max Planck Fellow in 2018. Now the researchers have identified a set of biomarkers in human blood which could be used in parallel in clinical studies and in ageing research on model organisms. The scientists searched in blood samples of 44,168 individuals for biomarkers that are indicative of a person’s remaining lifespan. After an extensive analysis, the scientists arrived at a set of 14 biomarkers which include for example, various amino acids – the building blocks of proteins – and levels of ‘good’ and ‘bad’ cholesterol, fatty acid balances and inflammation. Clinical studies The blood-based measurement is intended as a first step towards a more personalised treatment of the elderly, explains study director Prof. Eline Slagboom. “As researchers on ageing, we are keen to determine the biological age. The calendar age just doesn’t say very much about the general state of health of elderly people: one 70-year-old is healthy, while another may already be suffering from three diseases. We now have a set of biomarkers which may help to identify vulnerable elderly people, who could subsequently be treated." Model organisms The set of biomarkers is also a starting point for parallel studies in model organisms. “Ageing research in model organisms is ahead of that in humans. To make use of that knowledge we need instruments to compare human and animal studies and this could be one. We are currently investigating if the identified substances can be found in the blood of typical model organisms such as mice and if they are affected by interventions in ageing.”, explains Slagboom. The researchers are now working on answering these questions together with the Cluster of Excellence for Aging Research at the University of Cologne. This large-scale study was possible through collaboration of LUMC with international biobanks, BBMRI-NL (Biobanking and BioMolecular resources Research Infrastructure the Netherlands) and the Max Planck Institute for Biology of Ageing in Cologne. Original publication Joris Deelen, Johannes Kettunen, Krista Fischer, Ashley van der Spek, Stella Trompet, Gabi Kastenmüller, Andy Boyd, Jonas Zierer, Erik B. van den Akker, Mika Ala-Korpela, Najaf Amin, Ayse Demirkan, Mohsen Ghanbari, Diana van Heemst, M. Arfan Ikram, Jan Bert van Klinken, Simon P. Mooijaart, Annette Peters, Veikko Salomaa, Naveed Sattar, Tim D. Spector, Henning Tiemeier, Aswin Verhoeven, Melanie Waldenberger, Peter Würtz, George Davey Smith, Andres Metspalu, Markus Perola, Cristina Menni, Johanna M. Geleijnse, Fotios Drenos, Marian Beekman, J. Wouter Jukema, Cornelia M. van Duijn, P. Eline Slagboom A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals Nature Communications, August 20th, 2019. DOI: 10.1038/s41467-019-11311-9

  • Brain Stimulation for PTSD Patients
    2380    

    NEWS

       |   14/08/2019    
    Brain Stimulation for PTSD Patients
    Medical & Healthcare  Health care equipment

    For 8-million adults who suffer from post-traumatic stress disorder in any given year, medication and cognitive therapy have been the treatment protocol. Now, University of Houston assistant professor of electrical engineering Rose T. Faghih is reporting in Frontiers in Neuroscience that a closed-loop brain stimulator, based on sweat response, can be developed not only for PTSD patients, but also for those who suffer an array of neuropsychiatric disorders. “Sweat primarily helps maintain body temperature; however, tiny bursts of sweat are also released in response to psychologically arousing stimuli. Tracking the associated changes in the conductivity of the skin, which can be seamlessly measured using wearables in real-world settings, thus provides a window into a person’s emotions,” reports Faghih. For people with movement disorders like Parkinson’s disease and essential tremor, who have not responded to medication, application of high-frequency electric current to the brain, or deep brain stimulation, is regarded as most effective. Electrodes are placed in certain areas of the brain to regulate abnormal functions and a pacemaker-like device, placed in the upper chest, controls the amount of stimulation the brain receives. Open-loop stimulators, the most widely-used, deliver continuous stimulation until manually re-adjusted by a physician. Closed-loop stimulators, which provide stimulation in response to biomarkers of pathologic brain activity, have been developed for movement disorders, but are yet to be explored for the treatment of neuropsychiatric disorders. Signaling the onset of a PTSD episode, skin develops the tiniest sheen of perspiration. That symptom of the body’s fight or flight response signals a change in the skin’s electrical conductivity and provides a window into the brain’s state of emotional arousal. Using skin conductance to create the framework for a deep brain stimulator seemed logical to Faghih after reviewing group studies of Vietnam combat veterans with PTSD. Among the findings, PTSD subjects had the largest skin conductance responses when confronted with combat-related words. In a similar study comparing Vietnam combat veterans with and without PTSD and non-combat controls, PTSD veterans had the highest baseline skin conductance levels. “Skin conductance additionally has the advantage of being easily measured with wearable devices that afford convenience, seamless integration into clothing and do not involve risk of surgically implanted sensors,” said Faghih. The ultimate goal will be to develop closed-loop prototypes that can eventually be used for treating patients in a variety of neuropsychiatric disorders. Faghih’s graduate researchers Dilranjan Wickramasuriya and Md. Rafiul Amin were first and second authors, respectively, of the article. This project was supported, in part, by a grant from the National Science Foundation.

  • Novel neck brace improves functions of ALS patients
    1955    

    NEWS

       |   14/08/2019    
    Novel neck brace improves functions of ALS patients
    Medical & Healthcare  Physical medicine

    A novel neck brace, which supports the neck during its natural motion, was designed by Columbia engineers. This is the first device shown to dramatically assist patients suffering from Amyotrophic Lateral Sclerosis (ALS) in holding their heads and actively supporting them during range of motion. This advance would result in improved quality of life for patients, not only in improving eye contact during conversation, but also in facilitating the use of eyes as a joystick to control movements on a computer, much as scientist Stephen Hawkins famously did. A team of engineers and neurologists led by Sunil Agrawal, professor of mechanical engineering and of rehabilitation and regenerative medicine, designed a comfortable and wearable robotic neck brace that incorporates both sensors and actuators to adjust the head posture, restoring roughly 70% of the active range of motion of the human head. Using simultaneous measurement of the motion with sensors on the neck brace and surface electromyography (EMG) of the neck muscles, it also becomes a new diagnostic tool for impaired motion of the head-neck. Their pilot study was published August 7 in the Annals of Clinical and Translational Neurology. The brace also shows promise for clinical use beyond ALS, according to Agrawal, who directs the Robotics and Rehabilitation (ROAR) Laboratory. "The brace would also be useful to modulate rehabilitation for those who have suffered whiplash neck injuries from car accidents or have from poor neck control because of neurological diseases such as cerebral palsy," he said. "To the best of my knowledge, Professor Agrawal and his team have investigated, for the first time, the muscle mechanisms in the neck muscles of patients with ALS. Their neck brace is such an important step in helping patients with ALS, a devastating and rapidly progressive terminal disease," said Hiroshi Mitsumoto, Wesley J. Howe Professor of neurology at the Eleanor and Lou Gehrig ALS Center at Columbia University Irving Medical Center who, along with Jinsy Andrews, assistant professor of neurology, co-led the study with Agrawal. "We have two medications that have been approved, but they only modestly slow down disease progression. Although we cannot cure the disease at this time, we can improve the patient's quality of life by easing the difficult symptoms with the robotic neck brace." Commonly known as Lou Gehrig's disease, ALS is a neurodegenerative disease characterized by progressive loss of muscle functions, leading to paralysis of the limbs and respiratory failure. Dropped head, due to declining neck muscle strength, is a defining feature of the disease. Over the course of their illness, which can range from several months to more than 10 years, patients completely lose mobility of the head, settling in to a chin-on-chest posture that impairs speech, breathing, and swallowing. Current static neck braces become increasingly uncomfortable and ineffective as the disease progresses. To test this new robotic device, the team recruited 11 ALS patients along with 10 healthy, age-matched subjects. The participants in the study were asked to perform single-plane motions of the head-neck that included flexion-extension, lateral bending, and axial rotation. The experiments showed that patients with ALS, even in the very early stages of the disease, use a different strategy of head-neck coordination compared to age-matched healthy subjects. These features are well correlated with clinical ALS scores routinely used by clinicians. The measurements collected by the device can be used clinically to better assess head drop and the ALS disease progression. "In the next phase of our research, we will characterize how active assistance from the neck brace will impact ALS subjects with severe head drop to perform activities of daily life," said Agrawal, who is also a member of Columbia University's Data Science Institute. "For example, they can use their eyes as a joystick to move the head-neck to look at loved ones or objects around them."

  • New computational method could advance precision medicine
    2023    

    NEWS

       |   13/08/2019    
    New computational method could advance precision medicine
    Medical & Healthcare  Medical Test Services

    Scientists have devised a new computational method that reveals genetic patterns in the massive jumble of individual cells in the body. The discovery, published in the journal eLife, will be useful in discerning patterns of gene expression across many kinds of disease, including cancer. Scientists worked out the formulation by testing tissue taken from the testes of mice. Results in hand, they’re already applying the same analysis to biopsies taken from men with unexplained infertility. Don Conrad Ph.D. (2019) Donald Conrad, Ph.D. “There have been very few studies that attempt to find the cause of any disease by comparing single-cell expression measurements from a patient to those of a healthy control. We wanted to demonstrate that we could make sense of this kind of data and pinpoint a patient’s specific defects in unexplained infertility,” said co-senior author Donald Conrad, Ph.D., associate professor and chief of the Division of Genetics in the Oregon National Primate Research Center at Oregon Health & Science University. Simon Myers, Ph.D., of the University of Oxford, also is a senior co-author. Conrad said he expects the new method will advance the field of precision medicine, where individualized treatment can be applied to the specific nuance of each patient’s genetic readout. The scientists made the breakthrough by applying a method recently developed at the University of Oxford to gene expression data from the massive trove of individual cells comprising even minuscule tissue biopsies. The method is known as sparse decomposition of arrays, or SDA. “Rather than clustering groups of cells, SDA identifies components comprising groups of genes that co-vary in expression,” the authors write. The new study applied the method to 57,600 individual cells taken from the testes of five lines of mice: Four that carry known genetic mutations causing defects in sperm production and one with no sign of genetic infertility. Researchers wanted to see whether it was possible to sort this massive dataset based on the variation in physiological traits resulting from differences in the genes expressed in the RNA, or ribonucleic acid, of individual cells. Researchers found they were able to cut through the statistical noise and sort many thousands of cells into 46 genetic groups. “It’s a data-reduction method that allows us to identify sets of genes whose activity goes up and down over subsets of cells,” Conrad said. “What we’re really doing is building a dictionary that describes how genes change at a single-cell level.” The work will immediately apply to male infertility. Infertility affects an estimated 0.5% to 1% of the male population worldwide. Current measures to treat male infertility involve focus on managing defects in the sperm itself, including through in vitro fertilization. However, those techniques don’t work in all cases. “We’re talking about the problem where you don’t make sperm to begin with,” Conrad said. This new technique could open new opportunities to diagnose a specific genetic defect and then potentially rectify it with new gene-editing tools such as CRISPR. Identification of a specific cause would be a vast improvement over the current state of the art in diagnosing male infertility, which amounts to a descriptive analysis of testicular tissue biopsies. “The opportunity provided by CRISPR, coupled to this kind of diagnosis, is really a match made in heaven,” Conrad said. This work was supported by National Institutes of Health grants R01HD078641 and R01MH101810; Wellcome Trust grants 098387/Z/12/Z and 212284/Z/18/Z and 109109/Z/15/Z. Research was further supported by the NIH Office of the Director to the Oregon National Primate Research Center, Award No. P510D011092.

  • Development of Simplified New Mass Spectrometric Technique u…
    2346    

    NEWS

       |   09/08/2019    
    Development of Simplified New Mass Spectrometric Technique u…
    Medical & Healthcare  Clinical Trial, Bioanalytical & Other Pharmaceutical Services

    A technology that can obtain high-resolution, micrometer-sized images for mass spectrometric analysis without sample preparation has been developed. DGIST Research Fellow Jae Young Kim and Chair-professor Dae Won Moon’s team succeeded in developing the precise analysis and micrometer-sized imaging of bio samples using a small and inexpensive laser. DGIST announced that Research Fellow Jae Young Kim in the Department of Robotics Engineering and Chair-professor Dae Won Moon’s team developed a technology that can analyze experiment samples without any preparation processing. Due to its ability to obtain high-resolution mass spectrometric images without an experimental environment using ‘continuous wave laser’1, the technology is expected to be applied widely in the precise medicine and medical diagnosis fields. Many advance preparations are needed for the mass spectrometric imaging of biometric samples using ‘specimen,’ which thinly cut an object to analyze. The specimen must be changed artificially since they cannot be analyzed accurately in a room temperature or atmospheric pressure. To develop a convenient analysis technology and ease the burden, Research Fellow Kim started the research. The research team installed a lens carrying continuous wave laser right below a microscope substrate where the specimen is put and shot the laser on it to measure mass spectra by examining molecules from desorption2. The mass spectra can be analyzed through a continuous wave laser whose energy is weaker than other lasers because of the use of ‘graphene substrate’ below the specimen. Since the honeycomb-patterned graphene has very high heat conductivity and can convert light into heat, it can secure enough heat needed for specimen analysis with small amount of light generated by the continuous wave laser. This technology is also advantageous for obtaining high-resolution analysis images, because it can secure space to observe specimen much more closely even when using a 20x magnifying lens. Chair-professor Dae Won Moon in the Department of New Biology explained that “Through this technology, we could greatly shorten the preparation time for analysis by omitting the specimen preprocessing step. Our next plan is to develop the technology further so it can be applied in various areas such as medical diagnosis.” This research was participated by Research Fellow Jae Young Kim in the Department of Robotics Engineering and Ph.D. candidate Heejin Lim in the Department of New Biology as the co-first authors and was conducted with Professor Cheol Song in the Department of Robotics Engineering at DGIST, Professor Dong-Kwon Lim at Korea University, and Research Professor Ji-Won Park at Chungnam National University. The results were published as the cover paper on “ACS Applied Materials & Interfaces,” an international journal in the chemical and nano-technology field, on July 31. 1 Continuous wave laser: Emits laser beam continuously, is smaller and cheaper than pulse-type laser, and has a simple structure. Also referred to as ‘CW laser.’ 2 Desorption: Molecules absorbed on a solid surface fall off from the surface due to heat, light, electronic shock, etc. For more information, contact: Dae Won Moon, Chair Professor Department of New Biology Daegu Gyeongbuk Institute of Science and Technology (DGIST) E-mail: dwmoon@dgist.ac.kr Associated Links Research Paper in Journal of ACS Applied Materials & Interfaces https://pubs.acs.org/doi/10.1021/acsami.9b02620 Journal Reference Jae Young Kim, Heejin Lim, Sun Young Lee, Cheol Song, Ji-Won Park, Hyeon Ho Shin, Dong-Kwon Lim, and Dae Won Moon, "Graphene-Coated Glass Substrate for Continuous Wave Laser Desorption and Atmospheric Pressure Mass Spectrometric Imaging of Live Hippocampal Tissue", ACS Applied Materials & Interfaces, Published on July, 2019.