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Tag: Nature (journal)

  • Sensor Alerts Food Spoilage in Real-Time

    Sensor Alerts Food Spoilage in Real-Time

    Newswise — Food waste and food-borne diseases are among the most critical problems urban populations face today. They contribute to greenhouse emissions tremendously and amplify economic and environmental costs. Since food spoilage remains the main reason for this waste, the circumstances of processing, transporting, and preserving food still need to be improved in line with current technological advancements. Current monitoring processes are conducted in laboratories and use expensive chromatographic devices. These not only require too much time but also excessive resources and qualified personnel. So, present methods unfortunately prove to be inefficient in today’s circumstances.

    New research published in Nature Food Magazine presents a significant alternative to this process: A new user-friendly, cost-effective, and up-to-date sensor that can be applied on food directly and replace lab-monitoring. The 2 x 2 cm miniature wireless device introduced in the paper offers real-time measurement, is battery-free and smartphone-compatible. It is expected to be highly effective especially in high-protein foods such as beef, chicken, and fish.

    The research was led by Dr. Emin İstif (Molecular Biology and Genetics, Kadir Has University) and Asst. Prof. Levent Beker (Mechanical Engineering, Koç University) with the contribution of Prof. İskender Yılgör and Dr. Emel Yılgör (Chemistry, Koç University), Asst. Prof. Çağdaş Dağ (Molecular Biology and Genetics, Koç University) and Asst Prof. Hatice Ceylan Koydemir (Texas A&M University). While existing solutions focus on the change in color of food, this new device, for the first time, offers a capacitive measurement method and thus utilizes near-field communication (NFC) technology with power-free and wireless communication. The authors indicate that this eliminates major disadvantages encountered in resistive devices such as moisture sensitivity and incorrect data due to distance.

    The invention will not only provide companies the opportunity of reducing costs but also help consumers tremendously. Once widely commercialized, the device will enable continuous monitoring on shelves and allow users to control freshness right before buying a product or even before consumption at home. This opportunity of on-demand spoilage analysis via mobile phones will ultimately help preventing food waste and food-borne diseases.

    With its cost-effectiveness and accessibility, the authors hope to contribute to the greater struggle against global warming and greenhouse emissions more effectively and quickly. The following steps will be to focus on increasing the potential for commercialization of the product in the near future.

    Koc University

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  • Earliest Levantine wind instruments found

    Earliest Levantine wind instruments found

    Newswise — Although the prehistoric site of Eynan-Mallaha in northern Israel has been thoroughly examined since 1955, it still holds some surprises for scientists. Seven prehistoric wind instruments known as flutes, recently identified by a Franco-Israeli team1, are the subject of an article published on 9 June in Nature Scientific Reports. The discovery of these 12,000 -year-old aerophones is extremely rare – in fact, they are the first to be discovered in the Near East. The “flutes”, made from the bones of a small waterfowl, produce a sound similar to certain birds of prey (Eurasian sparrowhawk and common kestrel) when air is blown into them. The choice of bones used to make these instruments was no accident – larger birds, with bigger bones that produce deeper sounds, have also been found at the site. The Natufians, the Near Eastern civilisation that occupied this village between 13,000 and 9,700 BC, deliberately selected smaller bones in order to obtain the high-pitched sound needed to imitate these particular raptors. The instruments may have been used for hunting, music or to communicate with the birds themselves. Indeed, it is clear that the Natufians attributed birds with a special symbolic value, as attested by the many ornaments made of talons found at Eynan-Mallaha. The village, located on the shores of Lake Hula, was home to this civilisation throughout its 3,000 years of existence. It is therefore of vital importance in revealing the practices and habits of a culture at the crossroads between mobile and sedentary lifestyles, and the transition from a predatory economy to agriculture. This work2 was supported by the Fyssen Fondation and the ministère des Affaires étrangères.

     

    Notes

    1. The team is co-directed by Laurent Davin (post-doctoral researcher at the Fyssen Fondation) and José-Miguel Tejero (University of Vienna, University of Barcelona) and includes scientists from the Centre de recherche français à Jérusalem (CNRS/Aix-Marseille Université/ministère de la Culture), the laboratoire Technologie et ethnologie des mondes préhistoriques (CNRS/Université Panthéon-Sorbonne/Université Paris Nanterre), The Hebrew University of Jerusalem (Institute of Archaeology), Israel Antiquities Authority, Virginia Commonwealth University (Department of Forensic Science), École Nationale Vétérinaire (Laboratoire d’Anatomie comparée, Nantes), the laboratoire Archéologies et sciences de l’Antiquité (CNRS/ministère de la Culture/Université Panthéon-Sorbonne/Université Paris Nanterre) and the l’Institut d’ethnologie méditerranéenne, européenne et comparative (CNRS/Université Aix-Marseille).
    2. Excavation of the Eynan-Mallaha site is still ongoing, under the direction of CNRS researcher Fanny Bocquentin and Israel Antiquities Authority researcher Lior Weisbrod.

    CNRS (Centre National de Recherche Scientifique / National Center of Scientific Research)

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  • Photosynthesis: Martian habitation & sustainable space travel

    Photosynthesis: Martian habitation & sustainable space travel

    Newswise — In a study published in Nature Communications, scientists assess a new technique which could convert renewable, green energy from outside the Earth’s atmosphere. They are taking advantage of photosynthesis – the chemical process plants undergo every day to create energy – to help the space industry become more sustainable.

    The research led by the University of Warwick evaluates the use of a special device known as semiconductor to absorb sunlight on Moon and Mars. It is hoped that the devices could promote Martian life support systems.

    These “artificial photosynthesis devices” undergo the same processes which keeps plants alive on Earth – they convert water into oxygen using only sunlight whilst recycling carbon dioxide. These integrated systems have the advantage of directly using solar power and could save on weight on long-term space travels in comparison to traditional systems currently in use on the International Space Station – making space travel more efficient.

    There is a need for efficient and reliable energy sources in space to enable the exploration of our solar system. It is hoped that the technology could be installed on the Moon and Mars to harvest green energy to help power rockets and complement life support systems for the production of oxygen and other chemicals as well as the recycling of carbon dioxide. The insights gained in this study with respect to improving device efficiencies also feed back into their optimization for Earth applications and also provide insights into the performance of traditional solar cells in space.

    Assistant Professor Katharina Brinkert, Department of Chemistry, said: “Human space exploration faces the same challenges as the green energy transition on Earth: both require sustainable energy sources. With sunlight being so abundantly available in space, we have shown how this source could be used to harvest energy – much like plants back on Earth – for life support systems for long-term space travel. The technology could provide ample oxygen production and carbon dioxide recycling on both Moon and Mars.”

    Associate Professor Sophia Haussener, at the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, added: “In this study, we finally quantify the potential of such devices for extra-terrestrial use and provide initial design guidelines for their potential implementation.”

    The research project was funded by the European Space Agency via the Open Space Innovation Platform – https://ideas.esa.int.

    University of Warwick

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  • Pigeons’ dreamscapes

    Pigeons’ dreamscapes

    Dreams have been considered a hallmark of human sleep for a long time. Latest findings, however, suggest that when pigeons sleep, they might experience visions of flight. Researchers at Ruhr University Bochum, Germany, and at the Max Planck Institute for Biological Intelligence studied brain activation patterns in sleeping pigeons, using functional magnetic resonance imaging.

    Ruhr-Universitat Bochum

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  • Scientists Use Machine Learning to ‘See’ How the Brain Adapts to Different Environments

    Scientists Use Machine Learning to ‘See’ How the Brain Adapts to Different Environments

    Newswise — Johns Hopkins scientists have developed a method involving artificial intelligence to visualize and track changes in the strength of synapses — the connection points through which nerve cells in the brain communicate — in live animals. The technique, described in Nature Methods, should lead, the scientists say, to a better understanding of how such connections in human brains change with learning, aging, injury and disease.

    “If you want to learn more about how an orchestra plays, you have to watch individual players over time, and this new method does that for synapses in the brains of living animals,” says Dwight Bergles, Ph.D., the Diana Sylvestre and Charles Homcy Professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University (JHU) School of Medicine.

    Bergles co-authored the study with colleagues Adam Charles, Ph.D., M.E., and Jeremias Sulam, Ph.D., both assistant professors in the biomedical engineering department, and Richard Huganir, Ph.D., Bloomberg Distinguished Professor at JHU and Director of the Solomon H. Snyder Department of Neuroscience. All four researchers are members of Johns Hopkins’ Kavli Neuroscience Discovery Institute.

    Nerve cells transfer information from one cell to another by exchanging chemical messages at synapses (“junctions”). In the brain, the authors explain, different life experiences, such as exposure to new environments and learning skills, are thought to induce changes at synapses, strengthening or weakening these connections to allow learning and memory. Understanding how these minute changes occur across the trillions of synapses in our brains is a daunting challenge, but it is central to uncovering how the brain works when healthy and how it is altered by disease.

    To determine which synapses change during a particular life event, scientists have long sought better ways to visualize the shifting chemistry of synaptic messaging, necessitated by the high density of synapses in the brain and their small size — traits that make them extremely hard to visualize even with new state-of-the-art microscopes.

    “We needed to go from challenging, blurry, noisy imaging data to extract the signal portions we need to see,” Charles says.

    To do so, Bergles, Sulam, Charles, Huganir and their colleagues turned to machine learning, a computational framework that allows flexible development of automatic data processing tools. Machine learning has been successfully applied to many domains across biomedical imaging, and in this case, the scientists leveraged the approach to enhance the quality of images composed of thousands of synapses. Although it can be a powerful tool for automated detection, greatly surpassing human speeds, the system must first be “trained,” teaching the algorithm what high quality images of synapses should look like.

    In these experiments, the researchers worked with genetically altered mice in which glutamate receptors — the chemical sensors at synapses — glowed green (fluoresced) when exposed to light. Because each receptor emits the same amount of light, the amount of fluorescence generated by a synapse in these mice is an indication of the number of synapses, and therefore its strength.

    As expected, imaging in the intact brain produced low quality pictures in which individual clusters of glutamate receptors at synapses were difficult to see clearly, let alone to be individually detected and tracked over time. To convert these into higher quality images, the scientists trained a machine learning algorithm with images taken of brain slices (ex vivo) derived from the same type of genetically altered mice. Because these images weren’t from living animals, it was possible to produce much higher quality images using a different microscopy technique, as well as low quality images — similar to those taken in live animals — of the same views.

    This cross-modality data collection framework enabled the team to develop an enhancement algorithm that can produce higher resolution images from low quality ones, similar to the images collected from living mice. In this way, data collected from the intact brain can be significantly enhanced and able to detect and track individual synapses (in the thousands) during multiday experiments. 

    To follow changes in receptors over time in living mice, the researchers then used microscopy to take repeated images of the same synapses in mice over several weeks. After capturing baseline images, the team placed the animals in a chamber with new sights, smells and tactile stimulation for a single five-minute period. They then imaged the same area of the brain every other day to see if and how the new stimuli had affected the number of glutamate receptors at synapses.

    Although the focus of the work was on developing a set of methods to analyze synapse level changes in many different contexts, the researchers found that this simple change in environment caused a spectrum of alterations in fluorescence across synapses in the cerebral cortex, indicating connections where the strength increased and others where it decreased, with a bias toward strengthening in animals exposed to the novel environment.

    The studies were enabled through close collaboration among scientists with distinct expertise, ranging from molecular biology to artificial intelligence, who don’t normally work closely together. But such collaboration, is encouraged at the cross disciplinary Kavli Neuroscience Discovery Institute, Bergles says. The researchers are now using this machine learning approach to study synaptic changes in animal models of Alzheimer’s disease, and they believe the method could shed new light on synaptic changes that occur in other disease and injury contexts.

    “We are really excited to see how and where the rest of the scientific community will take this,” Sulam says.

    The experiments in this study were conducted by Yu Kang Xu (a Ph.D. student and Kavli Neuroscience Discovery Institute fellow at JHU), Austin Graves, Ph.D. (assistant research professor in biomedical engineering at JHU) and Gabrielle Coste (neuroscience Ph.D. student at JHU). This research was funded by the National Institutes of Health (RO1 RF1MH121539).

    Johns Hopkins Medicine

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  • Ancient viruses found in coral symbionts’ DNA

    Ancient viruses found in coral symbionts’ DNA

    Newswise — HOUSTON – (June 1, 2023) –A group of marine biologists from various countries has made a remarkable finding, uncovering the traces of ancient RNA viruses integrated into the DNA of symbiotic organisms residing within coral reefs.

    In a groundbreaking revelation, it has been revealed that the RNA fragments derived from viruses had infected the symbiotic organisms as far back as 160 million years. The astonishing discovery, highlighted in a recent open-access publication in the journal Communications Biology by Nature, holds immense potential for enhancing our understanding of the ongoing battle against viral infections in corals and their associated organisms. This finding has taken scientists by surprise since the integration of RNA viruses into the DNA of their host organisms is an uncommon phenomenon.

    Through the study, it has been revealed that endogenous viral elements (EVEs) are prevalent in the genetic makeup of coral symbionts. These symbionts, known as dinoflagellates, are single-celled algae residing within corals, imparting vibrant colors to their hosts. The identification of EVEs reinforces recent findings that viruses, not limited to retroviruses, have the ability to incorporate fragments of their genetic material into the genomes of their host organisms.

    “Then how did it happen?” inquired Adrienne Correa, one of the co-authors of the study from Rice University. She further explained, “While it might seem accidental, researchers are increasingly discovering that such occurrences are more common than previously thought. These ‘accidents’ have been identified in various hosts, ranging from bats and ants to plants and algae.”

    The presence of an RNA virus within coral symbionts came as an unexpected revelation.

    “I found this project particularly intriguing,” expressed Alex Veglia, the lead author of the study and a graduate student in Correa’s research team. Veglia continued, “Based on our current understanding, there is truly no logical explanation for the presence of this virus within the genome of the symbionts.”

    The research, funded by the Tara Ocean Foundation and the National Science Foundation, was spearheaded by Correa, Veglia, along with two scientists from Oregon State University: postdoctoral scholar Kalia Bistolas and marine ecologist Rebecca Vega Thurber. By unraveling crucial insights, this study offers valuable clues for scientists to enhance their comprehension of the ecological and economic ramifications of viruses on reef well-being.

    During their investigation, the researchers did not detect any endogenous viral elements (EVEs) derived from RNA viruses in the samples of filtered seawater or within the genomes of dinoflagellate-free stony corals, hydrocorals, or jellyfish. However, EVEs were found extensively in coral symbionts gathered from numerous coral reef locations. This indicates that the pathogenic viruses were, and likely still are, selective in their choice of target hosts.

    Correa, an assistant professor of biosciences, emphasized the vast diversity of viruses that exist on our planet. She explained, “While we have extensive knowledge about certain viruses, the majority of viruses remain uncharacterized. We may be able to detect their presence, but we are still unaware of their host organisms.”

    Correa highlighted the various methods by which viruses, including retroviruses, can replicate through host infections. She stated, “One intriguing aspect of our study is that this RNA virus is not classified as a retrovirus. Considering this, one wouldn’t anticipate it to integrate into the host’s DNA.”

    Correa remarked, “Over the past several years, we have observed a multitude of viruses within coral colonies, but it has been challenging to definitively determine their specific targets.” She further stated, “Therefore, this discovery provides us with the most reliable and conclusive data regarding the actual host of a virus associated with coral colonies. With this knowledge in hand, we can now delve into understanding why the symbiont retains that DNA or a portion of the genome. The question arises: Why hasn’t it been lost over time?”

    The revelation that the endogenous viral elements (EVEs) have been preserved over millions of years implies that they might hold some advantageous role for the coral symbionts. It also suggests the existence of a mechanism that actively promotes the genomic integration of EVEs.

    Veglia expressed the multitude of possibilities for further exploration, such as investigating whether these elements serve as antiviral mechanisms within dinoflagellates and assessing their potential impact on reef health, particularly in the context of rising ocean temperatures.

    Veglia raised important questions related to the potential influence of rising seawater temperatures on the presence of endogenous viral elements (EVEs) within Symbiodiniaceae species. He pondered whether the presence of EVEs in their genomes enhances their ability to combat infections caused by present-day RNA viruses. These queries emphasize the need for further research to unravel the intricate connections between EVEs, symbiont genomes, and the response to viral infections under changing environmental conditions.

    “In another study, we demonstrated that there is a rise in RNA viral infections during episodes of thermal stress in corals. Hence, there are numerous interconnected factors at play. The current discovery provides another valuable piece to complete the puzzle,” Veglia explained. The intricate relationship between thermal stress, viral infections, and coral health requires comprehensive examination to gain a holistic understanding of the dynamics involved.

    Correa cautioned against making assumptions about the virus having a negative impact, but she also noted that there is evidence suggesting its increased productivity under conditions of temperature stress. This highlights the complexity of the situation and the need for further investigation to better understand the potential effects of the virus on coral health.

    Thurber holds the distinguished position of Emile F. Pernot Professor in the Department of Microbiology at Oregon State University.

    The study included more than 20 co-authors from the University of Konstanz, Germany; the Institute of Microbiology and Swiss Institute of Bioinformatics, Zürich; the University of Perpignan, France; the Scientific Center of Monaco; the Université Paris-Saclay, Evry, France; the Tara Ocean Foundation, Paris; the University of Maine; Sorbonne University, France; the University of Tsukuba, Japan; Paris Science and Letters University, France; the University of Paris-Saclay; the Weizmann Institute of Science, Rehovot, Israel; Côte d’Azur University, Nice, France; the European Bioinformatics Institute, University of Cambridge, England; Ohio State University; and the National University of Ireland, Galway.

    National Science Foundation support was provided by three grants (2145472, 2025457, 1907184).

    -30-

    Peer-reviewed paper:

    “Endogenous viral elements reveal associations between a non-retroviral RNA virus and symbiotic dinoflagellate genomes” | Communications Biology | DOI: 10.1038/s42003-023-04917-9

    Authors: Alex J. Veglia, Kalia S.I. Bistolas, Christian R, Voolstra, Benjamin C. C. Hume, Hans-Joachim Ruscheweyh, Serge Planes, Denis Allemand, Emilie Boissin, Patrick Wincker, Julie Poulain, Clémentine Moulin, Guillaume Bourdin, Guillaume Iwankow, Sarah Romac, Sylvain Agostini, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Colomban de Varga, Eric Douville, Michel Flores, Didier Forcioli, Paola Furla, Pierre Galand, Eric Gilson, Fabien Lombard, Stéphane Pesant, Stéphanie Reynaud, Matthew B. Sullivan, Shinichi Sunagawa, Olivier Thomas, Romain Troublé, Didier Zoccola, Adrienne M.S. Correa, and Rebecca L. Vega Thurber

    https://doi.org/10.1038/s42003-023-04917-9

     

     

    Rice University

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  • Pan-cancer T cell atlas reveals new details of tumor microenvironment

    Pan-cancer T cell atlas reveals new details of tumor microenvironment

    Newswise — HOUSTON ― A new study led by researchers at The University of Texas MD Anderson Cancer Center, published today in Nature Medicine, provides a deeper understanding of the vast diversity of T cell states as well as their relationships and roles within the complex tumor microenvironment, bringing a fresh perspective to understanding immunotherapy efficacy in cancer.

    Recent studies have shown that the phenotypic states of T cells, as well as their relative proportions, play a crucial role in determining the effectiveness of immunotherapy and the likelihood of potential adverse effects. This new pan-cancer single-cell T cell atlas integrates 27 single-cell RNA sequencing datasets, including nine unique datasets from MD Anderson, covering 16 cancer types. It is the most detailed picture to date of the heterogeneity of T cells present within the tumor microenvironment.

    “This kind of large dataset and comprehensive pan-cancer analysis provides the opportunity to see things that aren’t visible when studying a single type of cancer or even a handful of cancer types,” said corresponding author Linghua Wang, M.D., Ph.D. associate professor of Genomic Medicine. “We hope these high-resolution maps, including the thoroughly characterized T cell states, are valuable resources for facilitating future T cell studies and biomarker discovery.”

    One notable discovery from this study is the previously undescribed T cell stress response state, or TSTR. In prior single-cell studies, these T cells often were overlooked or considered to be artifacts related to tissue dissociation. However, with the extensive data available, the researchers were able to identify these cells as a clearly unique group, distinct from other CD4+ or CD8+ T cell subsets, and to validate their existence in situ using multiple spatial profiling methods.

    TSTR cells can be thought of as ‘stressed out’ T cells and, just like a stressed person might be less effective at their job, they seem to be less effective at fighting cancer. While both TSTR cells and exhausted T cells may be dysfunctional, TSTR cells appear to follow a unique differentiation path, distinct from the trajectory of exhausted T cells.

    TSTR cells are characterized by high heat shock gene expression and, importantly, are seen at significantly higher fractions in both CD4+ and CD8+ T cells following immune checkpoint blockade therapy, particularly in non-responders. This suggests TSTR cells may play a role in resistance to immunotherapy. This new T cell state adds an additional layer to our understanding of the intricate biology of cancer and provides a potential target for future therapies.

    “The fact that these TSTR cells are found in many different types of tumors opens up a whole new world of possibilities that could have high translational potential,” Wang said. “Investigating the mechanistic causes of stress response in T cells, understanding how these stressed T cells are induced in the tumor microenvironment, and learning how to stop or reverse this TSTR state could catalyze the development of more effective therapeutic strategies that may bring the benefit of immunotherapy to more cancer patients.”

    This work also underscores the value of large, integrative datasets in oncology. This pan-cancer T cell atlas exemplifies the power of big data to unravel the complex landscape of T cells within tumors. The researchers described a total of 32 T cell states in this study, and further identified seven subpopulations within the CD4+ regulatory subset, five within the CD4+ follicular helper T cell population, and eight states among proliferating T cells.

    These findings all highlight the extensive heterogeneity of T cell states within the tumor microenvironment and the need to further understand how these states contribute to disease progression and immunotherapy response.

    “There are still many questions left to answer,” Wang said. “One of the limitations of this study is we don’t have the corresponding T cell receptor data for most of the datasets analyzed. We are not sure what triggers the TSTR state, and we don’t know from which T cell subset(s) they originate. It also is unclear whether these TSTR cells are specific to tumor cells and how they communicate with and influence other cells within the tumor microenvironment.”

    The research team has shared their T cell atlas with the wider research community through the Single-Cell Research Portal, a user-friendly, interactive web portal. This portal, developed by the team, allows both internal and external users to visualize and query the atlas without the need for bioinformatics skills.

    The team has also developed a tool named TCellMap, which enables researchers to automatically annotate T cells from their datasets by aligning with the high-resolution T cell maps generated by this study. Wang expressed her hope that these resources will prove valuable to scientists aiming to perform an in-depth analysis of T cells, leading to further discoveries and ultimately enhancing strategies for T cell therapy.

    Dr. Yanshuo Chu, Ph.D., from the Wang laboratory led the data analysis. This research was supported by MD Anderson, the National Institutes of Health/National Cancer Institute (R01CA266280, U01CA264583, P50CA016672, T32CA217789), the Cancer Prevention and Research Institute of Texas (CPRIT) and the U.S. Department of Defense. A full list of collaborating authors and their disclosures can be found with the full paper here.

    University of Texas MD Anderson Cancer Center

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  • Semiconductor quantum dots create dream material

    Semiconductor quantum dots create dream material

    Newswise — Researchers from the RIKEN Center for Emergent Matter Science and collaborators have succeeded in creating a “superlattice” of semiconductor quantum dots that can behave like a metal, potentially imparting exciting new properties to this popular class of materials.

    Semiconducting colloidal quantum dots have garnered tremendous research interest due to their special optical properties, which arise from the quantum confinement effect. They are used in solar cells, where they can improve the efficiency of energy conversion, biological imaging, where they can be used as fluorescent probes, electronic displays, and even quantum computing, where their ability to trap and manipulate individual electrons can be exploited.

    However, getting semiconductor quantum dots to efficiently conduct electricity has been a major challenge, impeding their full use. This is primarily due to their lack of orientational order in assemblies. According to Satria Zulkarnaen Bisri, lead researcher on the project, who carried out the research at RIKEN and is now at the Tokyo University of Agriculture and Technology, “making them metallic would enable, for example, quantum dot displays that are brighter yet use less energy than current devices.”

    Now, the group has published a study in Nature Communications that could make a major contribution to reaching that goal. The group, led by Bisri and Yoshihiro Iwasa of RIKEN CEMS, has created a superlattice of lead sulfide semiconducting colloidal quantum dots that displays the electrical conducting properties of a metal.

    The key to achieving this was to get the individual quantum dots in the lattice to attach to one another directly, “epitaxially,” without ligands, and to do this with their facets oriented in a precise way.

    The researchers tested the conductivity of the material they created, and as they increased the carrier density using a electric-double-layer transistor, they found that at a certain point it became one million times more conductive than what is currently available from quantum dot displays. Importantly, the quantum confinement of the individual quantum dots was still maintained, meaning that they don’t lose their functionality despite the high conductivity.

    “Semiconductor quantum dots have always shown promise for their optical properties, but their electronic mobility has been a challenge,” says Iwasa. “Our research has demonstrated that precise orientation control of the quantum dots in the assembly can lead to high electronic mobility and metallic behavior. This breakthrough could open up new avenues for using semiconductor quantum dots in emerging technologies.”

    According to Bisri, “We plan to carry out further studies with this class of materials, and believe it could lead to vast improvements in the capabilities of quantum dot superlattices. In addition to improving current devices, it could lead to new applications such as true all-QD direct electroluminescence devices, electrically driven lasers, thermoelectric devices, and highly sensitive detectors and sensors, which previously were beyond the scope of quantum dot materials.”

    In addition to RIKEN, the team included researchers from Tokyo Institute of Technology, the University of Tokyo, SPring-8, and the Tokyo University of Agriculture and Technology.

    RIKEN

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  • Chemical ‘supercharger’ solves molecular membrane mystery

    Chemical ‘supercharger’ solves molecular membrane mystery

    More than 60% of market drugs aimed at fighting disease target molecular proteins in the cell membranes – but techological limitations have previously limited researchers’ ability to observe these proteins in their natural environment.

    Now, scientists in the lab of Yale School of Medicine’s Kallol Gupta, PhD, have identified a class of chemicals, called “superchargers,” that gently destabilize the cell membrane while leaving cell proteins intact. The team was able to show how cell membranes regulate the speed of neurotransmitter release, a key step in central nervous system signaling.

    Traditional methods of isolating proteins from the membrane environment with mass spectrometry have damaged the proteins and their ability to bind with other molecules – including those with potentially therapeutic value. This breakthrough technology will allow scientists to screen future therapeutics precisely and directly at the point where proteins encounter new drugs.

     

    Yale University School of Medicine

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  • Epigenetic landscape modulates pioneer transcription factor binding

    Epigenetic landscape modulates pioneer transcription factor binding

    Newswise — Memphis, Tenn.—May 24, 2023) Like thread tightly wrapped around a spool, DNA is wrapped around histones and packaged into structures called nucleosomes. Scientists at St. Jude Children’s Research Hospital are exploring how a type of transcription factor called a pioneer transcription factor accesses DNA even when it is tightly wound. Their work revealed how the epigenetic landscape influences transcription factor binding. Problems with transcription have been implicated in numerous cancers, so this more detailed understanding of the process may aid in developing future therapeutics. The study was published today in Nature.  

    The nucleosome packaging of DNA can physically block transcription factors that regulate gene expression from accessing their binding sites. Restricting access to DNA is an integral part of how transcription is regulated. However, pioneer transcription factors can bind to their target piece of DNA even within compacted chromatin and are also known to promote the binding of other transcription factors. 

    Among pioneer transcription factors are the so-called Yamanaka factors which include Oct4 and are used to induce pluripotency (the ability to give rise to different cell types). How pioneer transcription factors access tightly wound DNA was unclear. To better understand the process, scientists at St. Jude used cryo-electron microscopy (cryo-EM) and biochemistry to investigate how Oct4 interacts with nucleosomes.  

    “Building on prior work to understand the dynamic behavior of nucleosomes, we wanted to understand how other factors might utilize those dynamic changes to access chromatin,” said corresponding author Mario Halic, Ph.D., St. Jude Department of Structural Biology. “Oct4 did not bind where we anticipated it might — rather than binding inside the nucleosome, we found that it bound a little bit outside.” 

    “One of the main findings is that epigenetic modifications can affect transcription factor binding and cooperativity,” Halic added. “The existing epigenetic state of chromatin can determine how transcription factors will cooperatively bind to chromatin.” 

    The epigenetic impact 

    Results show that the first Oct4 molecule binding “fixes” the nucleosome in a position that increases the exposure of other binding sites, thus promoting the binding of additional transcription factors and explaining transcription factor cooperativity. They also found that Oct4 contacts histones, and these interactions promote chromatin opening and influence cooperativity. Their work also showed that modifications at histone H3K27 affect the positioning of DNA by Oct4. These findings explain how the epigenetic landscape can regulate Oct4 activity to ensure proper cell programming.  

    Notably, the researchers used endogenous human DNA sequences instead of artificial sequences to assemble their nucleosomes. This allowed them to study the dynamic nature of the nucleosome, despite it being more challenging to work with.  

    “In this work, we used real genomic DNA sequences to study transcription factors in the context of where they function,” said first author Kalyan Sinha, Ph.D., St. Jude Department of Structural Biology. “This strategy allowed us to discover that the first binding event of Oct4 positions the nucleosomal DNA in a manner that allows cooperative binding of additional Oct4 molecules to internal sites. In addition, we observed exciting interactions with histone tails and have seen that histone modifications can alter those interactions. Together, these findings provide new insights into the pioneering activity of Oct4.” 

    “Histone modifications affect how DNA is positioned and how transcription factors can bind cooperatively,” Sinha added, “which means in cells, if you have the same DNA sequence, different epigenetic modifications can result in different, combinatorial effects on transcription factor binding.” 

    Authors and funding 

    The study’s other authors are Silvija Bilokapic, Yongming Du and Deepshikha Malik of St. Jude. 

    The study was supported by the National Institutes of Health (1R01GM135599-01 and 1R01GM141694-01) and ALSAC, the fundraising and awareness organization of St. Jude.  

     

      

    St. Jude Children’s Research Hospital 

    St. Jude Children’s Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read St. Jude Progress blog, and follow St. Jude on social media at @stjuderesearch. 

    St. Jude Children’s Research Hospital

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  • Ribosomal jam: Heartbreaking traffic

    Ribosomal jam: Heartbreaking traffic

    Newswise — Fukuoka, Japan—A team of researchers have discovered that a mutation in a ribosomal protein found specifically in heart and skeletal muscle leads to impaired cardiac contractility in mice.

    The mutation was found to delay the rate of translating mRNA, leading to ribosomes colliding and causing protein folding abnormalities. The abnormal proteins would then be targeted and degraded by the cell’s quality control system. Moreover, while the deficiency in the ribosomal protein, known as RPL3L, altered translation dynamics for the entire tissue, its effects were most pronounced for proteins related cardiac muscle contraction.

    The study, published in Nature Communications, shines new insight into the dynamics of a molecule as fundamental as ribosomes. Furthermore, since RPL3L gene deficiencies have been found in humans with cardiomyopathy and atrial fibrillation, the team hopes their new findings can lead to future treatments.

    You are likely familiar with the process of how cells produce the proteins and molecules that make the body function. DNA is transcribed into messenger RNA, or mRNA, which is then used as a blueprint to link amino acids together and build a protein. At the heart of the protein building process is the ribosome which reads the mRNA and translates that code into proteins.

    Because of its fundamental function, ribosomes are found within all cells and were thought to be generally the same. However, recent studies have revealed the existence of differences in ribosomal structures.

    “These differences in a ribosomal structure have shown to lead to translation specificity. For example, some ribosomes are better at producing proteins that control metabolism, or the cell cycle. It’s a new concept called Ribosome Heterogeneity,” explains Keiichi I. Nakayama of Kyushu University’s Medical Institute of Bioregulation who led the study. “We hypothesized that this heterogeneity exists between tissues. After screening for tissue-specific ribosomal proteins we found one that was only expressed in heart and skeletal muscle: RPL3L.”

    To elucidate the function of RPL3L, the team studied the hearts of mice with a mutated RPL3L gene. As expected, echocardiographic analysis showed that they had reduced cardiac contractility. Their next step was to study why exactly this mutation led to such a condition. As it turns out, the RPL3L mutation was causing a ‘translational traffic jam’ for proteins critical in proper heart function.

    “We found that the mutant RPL3L would delay translation for the proline and alanine codons on mRNA. This delay caused ribosomes to collide, resulting in proteins not folding correctly,” continues Nakayama. “Misfolded proteins would then be cleared out from the cell by its quality control system. More importantly, much of the misfolded proteins were ones involved in cardiac contraction.”

    The team hopes that by deepening our understanding of the translation dynamics of ribosome such as RPL3L, they can better understand how its genetic mutations—found in patients with dilated cardiomyopathy and atrial fibrillation—can lead to heart disease.

    “We are developing new understandings in the field of biology and medicine every day, even in something as fundamental as ribosomes. I’m exciting to see what we’ll find next,” concludes Nakayama.

    ###

    For more information about this research, see “RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function,” Chisa Shiraishi, Akinobu Matsumoto, Kazuya Ichihara, Taishi Yamamoto, Takeshi Yokoyama, Taisuke Mizoo, Atsushi Hatano, Masaki Matsumoto, Yoshikazu Tanaka, Eriko Matsuura-Suzuki, Shintaro Iwasaki, Shouji Matsushima, Hiroyuki Tsutsui, Keiichi I. Nakayama Nature Communications, https://doi.org/10.1038/s41467-023-37838-6

    About Kyushu University 
    Kyushu University is one of Japan’s leading research-oriented institutes of higher education since its founding in 1911. Home to around 19,000 students and 8,000 faculty and staff, Kyushu U’s world-class research centers cover a wide range of study areas and research fields, from the humanities and arts to engineering and medical sciences. Its multiple campuses—including one of the largest in Japan—are located around Fukuoka City, a coastal metropolis on the southwestern Japanese island of Kyushu that is frequently ranked among the world’s most livable cities and historically known as Japan’s gateway to Asia. Through its Vision 2030, Kyushu U will ‘Drive Social Change with Integrative Knowledge.’ Its synergistic application of knowledge will encompass all of academia and solve issues in society while innovating new systems for a better future.

    Kyushu University

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  • Engineering: Diapers to Houses

    Engineering: Diapers to Houses

    Newswise — Up to eight percent of the sand in concrete and mortar used to make a single-story house could be replaced with shredded used disposable diapers without significantly diminishing their strength, according to a study published in Scientific Reports. The authors suggest that disposable diaper waste could be used as a construction material for low-cost housing in low- and middle-income countries.

    Disposable diapers are usually manufactured from wood pulp, cotton, viscose rayon, and plastics such as polyester, polyethylene, and polypropylene. The majority are disposed of in landfill or by incineration.

    Siswanti Zuraida and colleagues prepared concrete and mortar samples by combining washed, dried, and shredded disposable diaper waste with cement, sand, gravel, and water. These samples were then cured for 28 days. The authors tested six samples containing different proportions of diaper waste to measure how much pressure they could withstand without breaking. They then calculated the maximum proportion of sand that could be replaced with disposable diapers in a range of building materials that would be needed to construct a house with a floorplan area of 36 square metres that complies with Indonesian building standards.

    The authors found that disposable diaper waste could replace up to ten percent of the sand needed for concrete used to form columns and beams in a three-story house. This proportion increased to 27 percent of sand needed for concrete columns and beams in a single-story house. Up to 40 percent of the sand needed for mortar in partition walls can be replaced with disposable diapers, compared to nine percent of the sand in mortar for floors and garden paving. Together, up to eight percent of the sand in all of the concrete and mortar building materials required to build a single-story house with a floorplan of 36 square metres can be replaced with disposable diaper waste — equivalent to 1.7 cubic metres of waste.

    The authors note that wider implementation of their findings would require the involvement of stakeholders in government and waste treatment in developing processes for the large-scale collection, sanitising, and shredding of diaper waste. Additionally, building regulations would need to be modified to allow the use of diaper waste as a construction material.

    ###

    Article details

    Application of non-degradable waste as building material for low-cost housing

    DOI: 10.1038/s41598-023-32981-y

    Scientific Reports

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  • Terrestrial World Outside Solar System Discovered, Covered in Volcanoes

    Terrestrial World Outside Solar System Discovered, Covered in Volcanoes

    Newswise — A large international team led by astronomers at the Trottier Institute for Research on Exoplanets at Université de Montréal (UdeM) today announced in the journal Nature the discovery of a new temperate world around a nearby small star.

    This planet, named LP 791-18 d, has a radius and a mass consistent with those of Earth. Observations of this exoplanet and another one in the same system indicate that LP 791-18 d is likely covered with volcanoes similar to Jupiter’s moon Io, the most volcanically active body in our Solar System.

    “The discovery of this exoplanet is an extraordinary find,“ said Professor Björn Benneke from UdeM’s Department of Physics. “The similarity in the properties of LP 791-18 d and Earth as well as the prospect of detectable geological activity and volcanism on it make it a key object to better understand how terrestrial worlds form and evolve.”

    Thanks to the very small size of the star – which is only slightly bigger than planet Jupiter – it should be possible to detect the atmosphere of this exoplanet, if it has one, using the James Webb Space Telescope. 

    A new terrestrial world in a multi-planetary system

    The planet discovery was led by Merrin Peterson, a graduate student in Benneke’s team at the Trottier Institute. It was found and studied using data from NASA’s Spitzer Space Telescope and Transiting Exoplanet Survey Satellite (TESS), as well as a suite of ground-based observatories all over the world.

    LP 791-18 d orbits a small red dwarf star about 86 light-years away in the southern constellation Crater. The Spitzer Telescope saw the star’s infrared light dim slightly when the planet passed in front of its disc a phenomenon called a transit. The observations of the system in October 2019 were among the last Spitzer collected before it was decommissioned.

    Benneke’s team used the data to determine that the planet is virtually the same size as Earth. With an orbital period of only 2.8 days, the exoplanet LP 791-18 d is located very close to its host star. However, the star is much smaller and less bright than our Sun. The temperature on LP-791-18 d is thus only slightly higher than on Earth.

    Astronomers have known about two other worlds in this system, planets LP 791-18 b and c, since 2019, when they were detected by the TESS satellite. Planet b is about 20% bigger than Earth and circles its star in a little less than a day, while Planet c is about 2.5 times Earth’s size and has a period of about 5 days. The newly found exoplanet d is thus the smallest in the family and orbits between planets b and c at an intermediate distance from the star. 

    Intense volcanic activity

    By precisely tracking the movement of the planet, the team realised that planets c and d pass very close to each other as they trace their orbits. At their closest, they are only 1.5 million kilometres apart, which is 33 times closer than Mars and Earth ever get to each other. Each close passage between the planets produces a gravitational tug on planet d, making its orbit less circular and more elliptical. Along this elliptical path, planet d is slightly deformed every time it goes around the star. The astronomers computed that this deformation produces a lot of heat in the interior of the planet that needs to be transported to the surface via intense volcanic activity. Due to this phenomenon called tidal heating, LP 791-18 d is likely carpeted with volcanoes.

    “The significant friction generated by tidal heating in the planet is responsible for heating its interior to a considerable extent, ultimately enabling the existence of a subsurface magma ocean,” explained Caroline Piaulet, an UdeM Ph.D. student who was involved in the discovery. “In our Solar System, we know that Jupiter’s moon Io is affected by Jupiter and its other moons in a similar way, and that world is the most volcanic we know.”

    Planet d sits on the inner edge of the temperate (or “habitable”) zone, the traditional range of distances from a star where scientists hypothesise liquid water could exist on a planet’s surface. If the planet is as geologically active as UdeM’s team suspects, it could maintain an atmosphere. Given the right conditions, temperatures could even drop low enough on the planet’s night side for water to condense on the surface.

    Measuring the masses of the planets

    The proximity of Planets c and d also helped scientists measure their masses. When approached by Benneke with this discovery, many members of the TESS Follow-up Observing Program turned their ground-based telescopes to the LP 791-18 system, allowing them to collect observations of 67 transits from Planets c and d. 

    In these data, the team at UdeM was able to detect transit timing variations, which are slight differences in the exact times of the planets’ transits caused by the gravitational tug they exert on each other. 

    “This technique allowed us to estimate the masses of Planets c and d using only the transit data,” Piaulet explained. “By combining this information with the size of the planets – an information readily available from the same data – we can estimate the density of the planets and thus get an idea of their composition and nature.”

    Comparing these values with planet interior models, astronomers were thus able to determine that the newly-found planet has a mass comparable to that of Earth. Its density is thus also consistent with a rocky composition like Earth. Planet c, which has a mass of about 7 times that of Earth’s, has probably retained a significant amount of gas or lighter materials, akin to Neptune’s composition.

    ‘Crucial to analyse the atmosphere’

    Planet c, the largest of the system, has already been approved for observing time on the Webb Telescope, as part of the Canadian NEAT program, dedicated to the study of exoplanets. Pierre-Alexis Roy, another Ph.D. student on Benneke’s team at UdeM, will be in charge of analysing these observations. “Having a precise constraint on the mass of Planet c will be crucial to analyse the substantial atmosphere we’re expecting to find on this mini-Neptune”, he explains. 

    In the future, the small size of the star may even allow the detection of a much less extended atmosphere on the newly found planet d. Scientists expect that an atmosphere like that of the Earth, Venus, or Saturn’s moon Titan could exist on Planet d. This system represents an unparalleled opportunity to learn more about small rocky planets, much like the TRAPPIST-1 system, which hosts seven Earth-sized planets, and is already being closely scrutinized by Webb.It is thus a prime target for Webb in the next few years that represents a similar opportunity to the TRAPPIST-1 system, which hosts seven Earth-sized planets. 

    “This system provides astronomers with a precious laboratory for testing various hypotheses related to the formation and evolution of terrestrial planets,” said Benneke. “The newly found planet d, an Earth-size world likely covered in volcanoes in a multiplanetary system, provides unprecedented opportunities to advance not only astronomy but many other fields of science, notably geology, planetary sciences, atmospheric sciences, and possibly astrobiology.”

    About this study

    “A temperate Earth-sized planet with tidally-heated interior transiting an M6 star” by Merrin Peterson et al., was published on May 17, 2023, in Nature.

    In addition to Merrin Peterson, Björn Benneke, Caroline Piaulet, and Pierre-Alexis Roy, members of the Trottier Institute for Research on Exoplanets at Université de Montréal, the team also includes Jonathan Gagné, an UdeM adjunct professor and scientific ddvisor at the Space for Life Montreal Planetarium and member of iREx; Mohamad Ali-Dib, a former Trottier postdoctoral fellow at iREx, now at NYU Abu Dhabi; Ryan Cloutier, a former iREx graduate student and now assistant professor at McMaster University; Lauren Weiss, a former Trottier postdoctoral fellow at iREx who is now assistant professor at the University of Notre Dame; as well as 66 other co-authors from the United States, France, Spain, Belgium, Japan and Morocco.  

    Source

    NASA Goddard Space Flight Center and the Trottier Institute for Research on Exoplanets – Université de Montréal

    University of Montreal

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  • New algorithm can predict diabetic kidney disease

    New algorithm can predict diabetic kidney disease

    Newswise — LA JOLLA, CALIF. – May 15, 2023 – Researchers from Sanford Burnham Prebys and the Chinese University of Hong Kong have developed a computational approach to predict whether a person with type 2 diabetes will develop kidney disease, a frequent and dangerous complication of diabetes. Their results, published in Nature Communications, could help doctors prevent or better manage kidney disease in people with type 2 diabetes.

    “This study provides a glimpse into the powerful future of predictive diagnostics,” says co-senior author Kevin Yip, Ph.D., a professor and director of Bioinformatics at Sanford Burnham Prebys. “Our team has demonstrated that by combining clinical data with cutting-edge technology, it’s possible to develop computational models to help clinicians optimize the treatment of type 2 diabetes to prevent kidney disease.”

    Diabetes is the leading cause of kidney failure worldwide. In the United States, 44% of cases of end-stage kidney disease and dialysis are due to diabetes. In Asia, this number is 50%.

    “There has been significant progress developing treatments for kidney disease in people with diabetes,” says co-senior author Ronald Ma, MB BChir, FRCP, a professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong. “However, it can be difficult to assess an individual patient’s risk for developing kidney disease based on clinical factors alone, so determining who is at greatest risk of developing diabetic kidney disease is an important clinical need.”

    The new algorithm depends on measurements of a process called DNA methylation, which occurs when subtle changes accumulate in our DNA. DNA methylation can encode important information about which genes are being turned on and off, and it can be easily measured through blood tests.

    “Our computational model can use methylation markers from a blood sample to predict both current kidney function and how the kidneys will function years in the future, which means it could be easily implemented alongside current methods for evaluating a patient’s risk for kidney disease,” says Yip.

    The researchers developed their model using detailed data from more than 1,200 patients with type 2 diabetes in the Hong Kong Diabetes Register. They also tested their model on a separate group of 326 Native Americans with type 2 diabetes, which helped ensure that their approach could predict kidney disease in different populations.

    “This study highlights the unique strength of the Hong Kong Diabetes Register and its huge potential to fuel further discoveries to improve our understanding of diabetes and its complications,” says study co-author Juliana Chan, M.D., FRCP, a professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong, who established the Hong Kong Diabetes Register more than two decades ago.

    “The Hong Kong Diabetes Register is a scientific treasure,” adds first author Kelly Yichen Li, Ph.D., a postdoctoral scientist at Sanford Burnham Prebys. “They follow up with patients for many years, which gives us a full picture of how human health can change over decades in people with diabetes.”

    The researchers are currently working to further refine their model. They are also expanding the application of their approach to look at other questions about human health and disease—such as determining why some people with cancer don’t respond well to certain treatments.

    “The science is still evolving, but we are working on incorporating additional information into our model to further empower precision medicine in diabetes,” adds Ma.

    ###

    Additional authors on the study include Claudia Ha Ting Tam, Cadmon King Poo Lim, Wing Yee So, Chuiguo Huang, Guozhi Jiang, Mai Shi, Hueng Man Lee, Hui-yao Lan and Cheuk-Chun Szeto, Chinese University of Hong Kong; Hongbo Liu, Katalin Susztak, University of Pennsylvania; Samantha Day, Robert L. Hanson and Robert G. Nelson, National Institute of Diabetes and Digestive and Kidney Diseases.

    The study was supported by grants from The Hong Kong Research Grants Council Theme-based Research Scheme (T12-402/13N) and Research Impact Fund (R4012-18), with additional support from the Research Grants Council (C4015-20E, C4045-18W, C4057-18E, C7044-19G, 14107420 and 14203119), National Institutes of Health (P30 CA030199-41, U54 AG079758-01, R21 AG075483-01S1, R01 DK087635, DK076077 and DK105821) and support from the Croucher Foundation and the Chinese University of Hong Kong.

    The study’s DOI is 10.1038/s41467-023-37837-7

    About Sanford Burnham Prebys

    Sanford Burnham Prebys is an independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 45 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children’s diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at SBPdiscovery.org or on Facebook facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

    About the Faculty of Medicine, The Chinese University of Hong Kong (CU Medicine)

    CU Medicine was set up to meet the needs of society by providing graduates with the professional development and knowledge that equips them to be caring and competent medical practitioners. As a young medical school established in 1981, the Faculty ranks top 3 in Asia and 32nd globally in the QS World University Rankings by Subject 2023.

    We have a team of over 1,200 full-time teaching and research staff from 19 departments/schools covering the entire range of research and clinical disciplines. We encourage collaborative working between scientists and clinicians across disciplines and specialties, and remain at the forefront of the translational medicine revolution. Our Faculty members excel in tackling challenging health problems, making a memorable impact on patients’ lives and the wider society.

    CU Medicine has won an internationally renowned research reputation for its encouraging environment for the effective pursuit of world-class research as well as remarkable contributions from team members.

    Sanford Burnham Prebys

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  • Gene editing, new DNA repair methods found

    Gene editing, new DNA repair methods found

    Newswise — (Santa Barbara, Calif.) — Gene editing is a powerful method for both research and therapy. Since the advent of the Nobel Prize-winning CRISPR/Cas9 technology, a quick and accurate tool for genome editing discovered in 2012, scientists have been working to explore its capabilities and boost its performance. 

    Researchers in UC Santa Barbara biologist Chris Richardson’s lab have added to that growing toolbox, with a method that increases the efficiency of CRISPR/Cas9 editing without the use of viral material to deliver the genetic template used to edit the target genetic sequence. According to their new paper published in the journal Nature Biotechnology, their method stimulates homology-directed repair (a step in the gene editing process) by approximately threefold “without increasing mutation frequencies or altering end-joining repair outcomes.”

    “We’ve found a chemical modification that improves non-viral gene editing and also discovered an intriguing new type of DNA repair,” Richardson said.

    Find, Cut and Paste

    The CRISPR/Cas9 method works by capitalizing on a defense technique employed by bacteria against viral attackers. To do this, the bacteria snip a piece of the invading virus’s genetic material, and incorporate it into their own in order to recognize it later. Should the bacteria get reinfected, they can target the now-familiar genetic sequences for destruction.

    In gene editing, this process uses the enzyme Cas9 as molecular “scissors” to snip sequences it recognizes, guided by the CRISPR system. This cut is also an opportunity to replace the severed genes with similar (homologous) but improved ones, utilizing the cell’s natural repair mechanisms. If successful, the cell should have modified expressions and functions thereafter.

    To deliver the repair template DNA to the nucleus of the cell where its genetic material lives, oftentimes viruses are used. While they are effective, the researchers say, viral workflows “are expensive, difficult to scale and potentially toxic to cells.”

    Nonviral templates are potentially less expensive and more scalable, although researchers still must overcome efficiency and toxicity barriers. In their study, the Richardson Lab found that introducing interstrand crosslinks into the workflow increased homology directed repair dramatically.

    “Every workflow that we have put this approach into has worked better by roughly threefold,” Richardson said.

    Interstrand crosslinks are lesions that keep the double strands of a DNA helix tethered to each other, making them unable to replicate. Cancer chemotherapies use this mechanism to interrupt tumor growth and kill cancer cells. Added to a homology directed repair template, however, these crosslinks were found to stimulate the cell’s natural repair mechanisms and increase the likelihood of editing success.

    “Basically, what we’ve done is taken this template DNA and damaged it,” Richardson said. “We’ve in fact damaged it in the most severe way I can think of. And the cell doesn’t say, ‘Hey this is junk; let me throw it away.’ What the cell actually says is, ‘Hey this looks great; let me stick it into my genome.’” The result is a highly efficient and minimally error-prone nonviral system of gene editing.

    Their discovery, like many breakthroughs in science, was actually something of a happy accident. While working to purify proteins to study DNA repair, graduate student researcher and lead author Hannah Ghasemi noted unanticipated changes to the outcomes of their experiments.

    “We were introducing these chemical modifications to the DNA templates in order to be able to pull them out of the cells and see what proteins were bound to them, and I was just checking to see if this modification had somehow affected the editing in any capacity,” she said. “I was expecting to either see no change or that it actually might have negatively affected the editing.”

    What she found instead was a positive effect, up to three times the editing activity of the uncrosslinked controls. Furthermore, the team found that even with the increase in edits — and therefore the chances for errors — there was no increase in mutation frequency. They are still investigating the specific mechanisms leading to this result, but they have ideas.

    “What we think happens is that the cell detects and tries to repair the damaged DNA that we’ve added this crosslink to,” Richardson said. “And in doing so, it delays the cell past a checkpoint where it would normally stop this recombination process. And so by prolonging the amount of time that it takes the cell to do this recombination, it makes it more likely that the edits will go to completion.” Studying this new process could also lead to a better understanding about how cells detect editing reagents and how they “decide” to accept them or not, he said.

    This method will find the most use in ex-vivo gene editing applications, according to the team, that is, in the realm of disease research and preclinical work.

    “We can more effectively knock down genes and insert things into genomes to study systems outside of the human body in a lab setting,” Ghasemi said. This development allows them to more efficiently build disease models and test hypotheses about how diseases work, which could lead to better clinical and therapeutic approaches.

    University of California, Santa Barbara

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  • Task-specific modulation of corticospinal neuron activity during motor learning in mice (Nature Communications)

    Task-specific modulation of corticospinal neuron activity during motor learning in mice (Nature Communications)

    Newswise — Learning motor skills depends on the brain’s ability to change, or be plastic. Specifically, the primary motor cortex of the brain can change as a person learns new motor tasks. When someone learns a complex task that involves fine motor control, like grasping an object, their brain undergoes large changes in the representation of the body part that controls the fine movements. In contrast, simpler tasks do not lead to such changes.

    In this study, researchers at Burke Neurological Institute investigated the role of a specific group of neurons, called corticospinal neurons, in learning and performing different motor tasks. Corticospinal neurons provide output from the brain directly to the spinal cord. The researchers used calcium imaging to measure activity in these neurons in mice as they learned to perform two different tasks: one that required precise movements of the forelimb, and another that was simpler and did not require as much precision.

    The researchers found that the activity of corticospinal neurons was different depending on the task the mice were performing. Specifically, the neurons showed patterns of activity that were associated with the timing of the precise movements required for the more complex task, but not for the simpler task. Further experiments showed that corticospinal neuron activity was necessary for performing the complex task, but not the simpler one.

    Overall, these findings suggest that the corticospinal network in the brain plays an important role in learning and executing precise motor movements. This research was supported by the Burke Foundation, the New York State Department of Health Spinal Cord Injury Research Board, the Craig H. Neilsen Foundation, and the National Institutes of Health.

    Burke Neurological Institute

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  • فهم سرعة اتصال الدماغ

    فهم سرعة اتصال الدماغ

    Newswise — مدينة روتشستر، ولاية مينيسوتا — في الغالب كان يُعتقد أن سرعة المعلومات المنقولة ما بين مناطق الدماغ تستقر في بداية المراهقة. لقد وجدت دراسة جديدة في مجلة نيتشر نيوروسينس أجراها باحثو مايو كلينك وزملاؤهم من هولندا أن سرعات نقل المعلومات تستمر في الزيادة حتى بداية البلوغ.

    نظرًا لأن مشاكل مثل: القلق والاكتئاب واضطرابات ثنائي القطب، يمكن أن تظهر في أواخر مرحلة المراهقة وبداية مرحلة البلوغ، فإن تحسين فهمنا لنمو الدماغ قد يساعد الأطباء على تقديم علاجات لهذه الاضطرابات.

    تقول دورا هيرميس، الحاصلة على الدكتوراه، مهندسة الطب الحيوي في مايو كلينك وكبيرة مؤلفي الدراسة: “قد يساعد الفهم الأساسي لمسار تطور دوائر الدماغ في تحديد فترات النمو الحساسة حيث يمكن للأطباء تقديم علاجات لمرضاهم”.

    يتطور النظام الهيكلي للمسارات العصبية في الدماغ أو الجهاز العصبي، الذي يُسمى الشبكة العصبية البشرية، مع تقدم الناس في السن. لكننا لا نملك وصفًا جيدًا لكيف تُؤثر التغييرات الهيكلية على سرعة الإشارات العصبية.

    توضح الدكتورة هيرميس قائلةً: “مثلما يعتمد وقت عبور الشاحنة على هيكل الطريق، فإن سرعة إرسال الإشارات بين مناطق الدماغ تعتمد على بنية المسارات العصبية. تنضج الشبكة العصبية البشرية خلال النمو والتقدم في العمر، ويمكن أن تتأثر بالمرض. قد تؤثر كل هذه العمليات على سرعة تدفق المعلومات إلى الدماغ. “في الدراسة، قامت الدكتورة هيرميس وزملاؤها بتحفيز أزواج من الأقطاب الكهربائية بنبضة كهربائية قصيرة لقياس الوقت الذي تستغرقه الإشارات للانتقال بين مناطق الدماغ لدى 74 مشاركًا في البحث تتراوح أعمارهم ما بين 4 و51 عامًا. تم إجراء قياسات داخل الجمجمة على مجموعة صغيرة من المرضى الذين لديهم مسارات كهربائية مزروعة لمراقبة الصرع في المركز الطبي الجامعي أوترخت، هولندا.

    أظهرت فترات تأخر الاستجابة في مناطق الدماغ المتصلة أن سرعات نقل المعلومات في الدماغ البشري تزداد طوال فترة الطفولة وحتى في بداية مرحلة البلوغ. وتكون الذروة في العمر من 30 إلى 40 عامًا تقريبًا.

    تشير بيانات الفريق إلى أن سرعات نقل البيانات لدى البالغين كانت أسرع مرتين تقريبًا مقارنة بالتي لدى الأطفال عادةً. كانت سرعات نقل المعلومات عادةً أسرع لدى الأشخاص ما بين 30 أو 40 عامًا مقارنةً بالمراهقين.

    تُقاس سرعة نقل المعلومات في الدماغ بالميلي ثانية، وهي وحدة زمنية تساوي واحدًا من الألف من الثانية. على سبيل المثال، وجد الباحثون أن قياس السرعة العصبية لمريض يبلغ من العمر 4 سنوات هو 45 مللي ثانية لإشارة واحدة لتنتقل من المناطق الأمامية إلى المناطق الجدارية في الدماغ. ولدى مريض يبلغ من العمر 38 عامًا، تم قياس نفس المسار فبلغ القياس 20 مللي ثانية. فقط للمقارنة، فإن طرفة العين تستغرق حوالي 100 إلى 400 مللي ثانية.

    ويعمل الباحثون على توصيف الاتصال الذي يبدؤه التحفيز الكهربائي في دماغ الإنسان. من الخطوات التالية هي فهم كيفية تغير سرعات نتقل الملعومات مع الأمراض العصبية بشكل أفضل. يتعاون الفريق مع جراحي أعصاب الأطفال وأطباء الأعصاب لفهم كيف تغيّر الأمراض من سرعات نتقل المعلومات بالمقارنة مع ما يمكن اعتباره ضمن النطاق الطبيعي لفئة عمرية معينة.

    تلقى البحث الدعم من المعهد الوطني للصحة العقلية التابع للمعاهد الوطنية للصحة (R01MH122258). لم يذكر الكاتبون أي إفصاحات ذات صلة. توجد قائمة كاملة بالمؤلفين والمؤسسات التي ينتمون إليها في مقال البحث.

    لمزيد من المعلومات، يرجى زيارة ديسكافريز إيدج.

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    نبذة عن مايو كلينك
    مايو كلينك هي مؤسسة غير ربحية تلتزم بالابتكار في الممارسات السريرية والتعليم والبحث وتوفير التعاطف والخبرة لكل مَن يحتاج إلى الاستشفاء والرد على استفساراته. لمعرفة المزيد من أخبار مايو كلينك، تفضَّل بزيارة شبكة مايو كلينك الإخبارية.

    Mayo Clinic

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  • New Method Uses Engineered Bacteria and AI to Sense and Record Environmental Signals

    New Method Uses Engineered Bacteria and AI to Sense and Record Environmental Signals

    Newswise — New York, NY—May 9, 2023—Researchers in Biomedical Engineering Professor Tal Danino’s lab were brainstorming several years ago about how they could engineer and apply naturally pattern-forming bacteria. There are many bacteria species, such as Proteus mirabilis (P. mirabilis), that self-organize into defined patterns on solid surfaces that are visible to the naked eye. These bacteria can sense several stimuli in nature and respond to these cues by “swarming”—a highly coordinated and rapid movement of bacteria powered by their flagella, a long, tail-like structure that causes a whip-like motion to help propel them. 

    For inspiration, Danino’s team at Columbia Engineering, which has a good deal of experience using synthetic biology methods to manipulate bacteria, discussed where else they might find similar patterns in nature and what their functions might be. They noted how tree rings record tree age and climate history, and that sparked their idea of applying P. mirabilis rings as a recording system. They had also been interested in applying AI to characterize the distinct features of bacterial colony patterns, an approach that they realized could then be used to decode an engineered pattern. 

    “This seemed to us to be an untapped opportunity to create a natural recording system for specific cues,” said Danino, a member of Columbia’s Data Science Institute (DSI).

    In a new study, published May 4 in Nature Chemical Biology, the researchers worked with P. mirabilis, commonly found in the soil and water and occasionally the human gut, known for its bullseye-appearing colony patterns. When the bacteria are grown on a Petri dish of a solid growth media, they alternate between phases of bacterial growth, which make visible dense circles, and bacterial movement, called “swarming” movement, which expands the colony outwards.  

    The team engineered the bacteria by adding what synthetic biologists call “genetic circuits”—systems of genetic parts, logically compiled to make the bacteria behave in a desired way. The engineered bacteria sensed the presence of the researchers’ chosen input—ranging from temperature to sugar molecules to heavy metals such as mercury and copper—and responded by changing their swarming ability, which visibly changed the output pattern.  

    Working with Andrew Laine, Percy K. and Vida L. W. Hudson Professor of Biomedical Engineering and a DSI member  and Jia Guo, assistant professor of neurobiology (in psychiatry) at the Columbia University Irving Medical Center the researchers then applied deep learning–a state-of-the-art AI technique–to decode the environment from the pattern, in the same way scientists look at the rings in a tree trunk to understand the history of its environment. They used models that can classify patterns holistically to predict, for example, sugar concentration in a sample, and models that can delineate or “segment” edges within a pattern to predict, for example, the number of times the temperature changed while the colony grew. 

    An advantage of working with P. mirabilis is that, compared to many of the typical engineered bacterial patterns, the native P. mirabilis pattern is visible to the naked eye without costly visualization technology and forms on a durable, easy-to-work-with solid agar medium. These properties increase the potential to apply the system as a sensor readout in a variety of settings. Using deep learning to interpret the patterns can enable researchers to extract information about input molecule concentrations from even complex patterns. 

    “Our goal is to develop this system as a low-cost detection and recording system for conditions such as pollutants and toxic compounds in the environment ,” said Anjali Doshi, the study’s lead author and a recent PhD graduate from Danino’s lab. “To our knowledge, this work is the first study where a naturally pattern-forming bacterial species has been engineered by synthetic biologists to modify its native swarming ability and function as a sensor.”

    Such work can help researchers better understand how the native patterns form, and beyond that, can contribute to other areas of biotechnology beyond the area of sensors. Being able to control bacteria as a group rather than as individuals, and control their movement and organization in a colony, could help researchers build living materials at larger scales, and help with the Danino lab’s parallel goal of engineering bacteria to be living “smart” therapeutics, by enabling better control of bacterial behaviors in the body. 

    This work is a new approach for building macroscale bacterial recorders, expanding the framework for engineering emergent microbial behaviors. The team next plans to build on their system by engineering the bacteria to detect a wider range of pollutants and toxins and moving the system to safe “probiotic” bacteria. Ultimately, they aim to develop a device to apply the recording system outside of the lab.

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    About the Study

    Journal: Nature Chemical Biology

    The study is titled “Engineered bacterial swarm patterns as spatial records of environmental inputs.”

    Authors are: Anjali Doshi 1 , Marian Shaw 1 , Ruxandra Tonea1 , Soonhee Moon1 , Rosalía Minyety1 , Anish Doshi2 , Andrew Laine1 , Jia Guo3,4 & Tal Danino 1,5,61 Department of Biomedical Engineering, Columbia University2 Department of Electrical Engineering and Computer Sciences, University of California, Berkeley3 Department of Psychiatry, Columbia University4 Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University5 Herbert Irving Comprehensive Cancer Center, Columbia University6 Data Science Institute, Columbia University

    This work was supported by an NSF CAREER Award (1847356 to T.D.), Blavatnik Fund for Innovations in Health (T.D.), and NSF Graduate Research Fellowship (A.D., Fellow ID 2018264757).

    A.D., M.S., J.G., A.L. and T.D. are named as inventors on a provisional patent application that has been filed by Columbia University with the US Patent and Trademark Office related to all aspects of this work. The remaining authors declare no competing interests. 

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    LINKS:

    Paper: https://www.nature.com/articles/s41589-023-01325-2
    DOI:  10.1038/s41589-023-01325-2

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    Columbia University School of Engineering and Applied Science

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  • First microbiome-targeting drug using CRISPR created by scientists

    First microbiome-targeting drug using CRISPR created by scientists

    Newswise — Many people have experienced infections from E. coli, which are primarily seen as inconvenient and unpleasant. For some patients, like those with blood cancer, however, there is a risk that the bacteria will travel into the bloodstream. In those cases, an E. coli infection is too often fatal. The mortality rate is 15-20%.

    The predominant cure for such infections is the use of antibiotics that have detrimental effects on the patient’s microbiome, which play a key part in our physical and emotional well-being, and other side effects. Furthermore, growing problems with antibiotic resistance render such treatments less effective in treating infections.

    An international team of scientists has now engineered the first published CRISPR-based candidate (see fact box) for a drug that targets E. coli directly and leaves the microbiome intact. A new paper in Nature Biotechnology titled ‘Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice’ describes the development of the drug candidate to a stage where it is ready for tests on humans.

    Through extensive use of synthetic biology, the team designed four bacterial viruses that use CRISPR technology to kill the unwanted bacteria precisely.

    “We believe that a narrow spectrum drug with these properties could be very useful to cancer patients, among others, who often get serious infections that are difficult to treat with current antibiotics,” says Morten Otto Alexander Sommer, a professor at DTU Biosustain, Co-founder of SNIPR Biome, and lead author of the paper.

    The work was carried out in collaboration with JAFRAL (Slovenia), JMI Laboratories (US), and Division of Infectuous Diseases at Weill Cornell Medicine (US).

    Engineering phages to target E. coli

    The team, primarily based at SNIPR Biome, screened a library of 162 naturally occurring phages (viruses that kill specific bacteria; see fact box). They found that eight of these phages showed promise in targeting E. coli. They then engineered the phages through gene editing to improve their ability to target E. coli.

    A cocktail of four of these phages, which they named SNIPR001, very effectively targeted bacteria in biofilms and reduced the number of E. coli in a manner that surpassed that of  naturally occurring phages. Further, they showed that the cocktail of phages was tolerated well in the gut of mice and mini pigs while reducing the emergence of E. coli. SNIPR001 is now in clinical development and has been granted a Fast-Track designation (expedited review) by the US Food and Drug Administration.

    FACT BOX: An overview of the SNIPR001 creation process:

    1. Naturally occurring phages are screened against a panel of E. coli strains.
    2. Phages with broad activity against E. coli are tail fibre engineered and/or armed with CRISPR–Cas systems containing sequences specific to E. coli, creating CAPs (Cas-armed phages).
    3. These CAPs are tested for host range, in vivo efficacy, and CMC specifications.

    SNIPR001 comprises four complementary CAPs and is a new precision antibiotic that selectively targets E.coli to prevent bacteremia in haematological cancer patients at risk of neutropenia (low levels of white blood cells).

    Blood cancer patients are first in line

    The reason this new development is exciting for blood cancer patients has to do with side effects stemming from their chemotherapy treatment. It causes the patient’s bone marrow to produce fewer blood cells and inflammation of the intestines. The latter increases the intestines’ permeability allowing bacteria from the gut to travel into the bloodstream. This combination of side effects leaves the patient vulnerable to infections from bacteria like E. coli. In such cases, the

    Today, patients at risk (i.e., with low levels of white blood cells) receive antibiotic treatments ahead of their chemotherapy, but in some cases, E. coli shows very high resistance to commonly used antibiotics. Also, the antibiotics themselves have several side effects that in some cases reduce the effect of the cancer treatments.

    “We need a wider variety of options available to treat these patients, preferably ones where we can specifically target the bacteria responsible to avoid side effects and that do not add to the problem of antibiotic resistance,” says Morten Otto Alexander Sommer.

    In recent years, researchers have been looking back towards using phages to treat infections because of the increase in antibiotic resistance. Before antibiotics were broadly available, phages were widely used and studied in countries that were then part of the Soviet Union. Still, there are few clinical trials, and the results haven’t been convincing, according to the paper.

    “Through emerging technologies like CRISPR, the use of phages in treating infections has become a viable pathway. As our results show, there is potential for enhancing naturally occurring phages through genetic engineering. It is my hope that this approach may also serve as a blueprint for new antimicrobials targeting resistant pathogens,” says Morten Otto Alexander Sommer.

    FACT BOX: CRISPR, phages, and phage therapy

    CRISPR technology is a way for scientists to edit DNA sequences in cells. It’s based on a defence mechanism bacteria naturally use to protect themselves. CRISPR technology uses a molecule called Cas9, which works like a pair of scissors to cut DNA at a specific spot.

    After the cut, the DNA can be fixed, or a new piece can be added. Scientists can use this tool to create genetically modified organisms, find new ways to treat genetic diseases, and learn more about how genes work.

    Phages are tiny viruses that can kill specific bacteria. They’re everywhere on Earth and help regulate bacterial populations and nutrient cycling. They infect and kill bacteria, and when the bacteria die, they release nutrients into the environment.

    Scientists use phages to treat bacterial infections, which is called phage therapy. They identify and isolate phages that can kill a specific bacterial strain and use them to fight infections caused by that strain.

    Phage therapy has some advantages to antibiotics, like targeting specific bacteria without side effects and potentially reducing antibiotic resistance.

    Technical University of Denmark (DTU)

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  • Archaea Diversity Drops in Warming Climate

    Archaea Diversity Drops in Warming Climate

    Newswise — Led by Jizhong Zhou, Ph.D., the director of the Institute for Environmental Genomics at the University of Oklahoma, an international research team conducted a long term experiment that found that climate warming reduced the diversity of and significantly altered the community structure of soil archaea. Their findings are published in the journal Nature Climate Change.

    At the microbiological level, life can be described as belonging to one of three kingdoms – how species are described in relation to one another. Eukarya contains complex organisms like animals and plants and microorganisms such as fungi. The other two categories, bacteria and archaea, are comprised only of microorganisms. Archaea are prevalent in a range of environments, from some of the most hostile like volcanoes and permafrost. However, archaea are also common in the human microbiome and as an important part of soil ecology.

    “As temperature is a major driver of biological processes, climate warming will impact various ecological communities,” Zhou said. “Based on long-term time-series data, our previous studies revealed that experimental warming leads to the divergent succession of soil bacterial and fungal communities, accelerates microbial temporal scaling, reduces the biodiversity of soil bacteria, fungi and protists, but increases bacterial network complexity and stability. However, how climate warming affects the temporal succession of the archaeal community remains elusive. Archaea are ubiquitously present in soil and are vital to soil functions, e.g., nitrification and methanogenesis.”

    Using a long-term multifactor experimental field site at OU’s Kessler Atmospheric and Ecological Field Station, the researchers showed that experimental warming of a tallgrass prairie ecosystem significantly altered the community structure of soil archaea and reduced their taxonomic and phylogenetic diversity. In contrast to the researchers’ previous observations in bacteria and fungi, their finds show that climate warming leads to convergent succession of the soil archaeal community, suggesting archaeal community structures would become more predictable in a warmer world.

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    About the Project

    The article, “Experimental Warming Leads to Convergent Succession of Grassland Archaeal Community” published May 3, 2023 in Nature Climate Change. DOI no. 10.1038/s41558-023-01664-x. Zhou, who is also a George Lynn Cross Research Professor of Microbiology in the Dodge Family College of Arts and Sciences, is the corresponding author. The first author is Ya Zhang, Institute for Environmental Genomics and Department of Microbiology and Plant Biology at OU. 

    About the University of Oklahoma Office of the Vice President for Research and Partnerships 

    The University of Oklahoma is a leading research university classified by the Carnegie Foundation in the highest tier of research universities in the nation. Faculty, staff and students at OU are tackling global challenges and accelerating the delivery of practical solutions that impact society in direct and tangible ways through research and creative activities. OU researchers expand foundational knowledge while moving beyond traditional academic boundaries, collaborating across disciplines and globally with other research institutions as well as decision makers and practitioners from industry, government and civil society to create and apply solutions for a better world. Find out more at ou.edu/research.

    University of Oklahoma

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