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Solving the puzzle of polymers binding to ice for Cryopreservation

Credit: Credit: University of Warwick Cryoprotectants are used to protect biological material during frozen storage They have to be removed

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  • Cryoprotectants are used to protect biological material during frozen storage
  • They have to be removed when defrosting, and how much to use and how exactly they inhibit ice recrystallisation is poorly understood
  • The polymer poly(vinyl)alcohol (PVA) is arguably the most potent ice recrystallisation inhibitor and researchers from the University of Warwick have unravelled how exactly it works.
  • This newly acquired knowledge base provides novel guidelines to design the next generation of cryoprotectants

When biological material (cells, blood, tissues) is frozen, cryoprotectants are used to prevent the damage associated with the formation of ice during the freezing process. New polymeric cryoprotectants are emerging, alongside the established cryoprotectants, but how exactly they manage to control ice formation and growth is still largely unknown. This is especially true for PVA, a deceptively simple synthetic polymer that interacts with ice by means of mechanisms that have now been revealed at the atomistic level thanks to researchers from the University of Warwick.

Cryoprotectants are crucial when freezing biological material to lessen the cellular damage involved with the formation of ice. Ice re-crystallization, that is the process by which larger ice crystals grow at the expense of smaller ones, is one of the major issues affecting the current cryopreservation protocols and it is still poorly understood. Researchers from the University of Warwick have investigated how a rather popular polymer with the potential to be used in cryopreservation binds to the growing ice crystals.

In the paper, ‘The atomistic details of the ice recrystallisation inhibition activity of PVA’, published in the journal Nature Communications, researchers from the University of Warwick have found that, contrary to the emerging consensus, shorter or longer polymeric chains of poly(vinyl)alcohol (PVA) all bind to ice.

Up to now, the community has been working under the assumption that short polymers do not bind strongly enough to the ice crystals, but in this work Dr. Sosso and co-workers have demonstrated that it is the subtle balance between these binding interactions and the effective volume occupied by the polymers at the interface with ice that determine their effectiveness in hindering ice re-crystallization.

This work brings together experimental measurements of ice recrystallization inhibition and computer simulations. The latter are invaluable tools to gain microscopic insight into processes such as the formation of ice, as they are able to see what is happening in very fast or very small processes which are hard to see via even the most advanced experimental techniques.

This work sheds new light onto the fundamental principles at the heart of ice re-crystallization, pinpointing design principles that can be directly harnessed to design the next generation of cryoprotectants. This achievement is a testament to the strength of what is affectionately known as ‘Team Ice’ at Warwick, an ever-growing collaborative network with the potential to make a huge impact on many aspects of ice formation, from atmospheric science to medicinal chemistry.

Fabienne Bachtiger, a PhD student working in the research group of Dr. Sosso (Department of Chemistry) who has spearheaded this work, explains:
“We have found that even rather short chains of PVA, containing just ten polymeric units, do bind to ice, and that small block co-polymers of PVA bind too. It is important for the experimental community to know this, as they have been working under different assumptions up to now. In fact, this means we can successfully use much smaller polymers than previously thought. This is crucial information to aid the development of new more active cryoprotectants.”

Dr. Gabriele Sosso, from the Department of Chemistry at the University of Warwick, who is leading a substantial computational effort to investigate the formation of ice in biological matter, points out that:
“With this contribution we have added a crucial piece to the puzzle of how exactly polymeric cryoprotectants interact with growing ice crystals. This is part of a larger body of computational and theoretical work that my group is pursuing with the intent to understand how cryoprotectants work at the molecular level, so as to identify designing principles that can be directly probed by our experimental colleagues. Warwick is the perfect place to further our understanding of ice, and this work showcases the impact of the very exciting collaboration between my research group and the Gibson Group.”

Professor Matthew Gibson, from the Department of Chemistry and Warwick Medical School at the University of Warwick adds: “Ice re-crystallization is a real challenge in cryobiology, leading to damage to cells but also in frozen foods or infrastructure. Understanding how even this ‘simple’ polymer works to control ice re-crystallization is a major step forward to discover new cryoprotectants, and ultimately to use them in the real world.”

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15 MARCH 2021

  • This newly acquired knowledge base provides novel guidelines to design the next generation of cryoprotectants
  • Source: https://bioengineer.org/solving-the-puzzle-of-polymers-binding-to-ice-for-cryopreservation/

    solving-the-puzzle-of-polymers-binding-to-ice-for-cryopreservation

    Bioengineer

    $1 million grant to address cold storage logistics in vaccine delivery

    Credit: Penn State College of Engineering COVID-19 vaccines have been tested, validated and administered to millions of people around the

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    COVID-19 vaccines have been tested, validated and administered to millions of people around the world. But in some countries, the vaccines have yet to arrive in great enough numbers.

    One significant hurdle is that the vaccines must be stored between 36 and 46 degrees Fahrenheit to retain their full efficacy, according to the Centers for Disease Control. To ensure the proper temperature, the vaccines need a refrigerated supply chain, also known as a cold chain, as they are distributed across the globe.

    “If they are in warm temperatures, COVID vaccines and other medications are susceptible to degradation, which means they lose potency,” said Medina, who heads the Medina Group Precision Therapeutics and Bioresponsive Materials Lab at Penn State. “And the cold storage supply chain is expensive to maintain, with several transport steps necessary from the manufacturer to the distributer to the provider facility.”

    To address that challenge, Medina and his team plan to develop fluorochemical dispersants, known as “FTags,” which coat the proteins within the vaccine liquids to stabilize them thermally.

    “The FTags dissolve the proteins in a fluorine-based liquid, which yields proteins that we believe may be stable at elevated temperatures, without compromising their structure or function,” Medina said. “When dissolved in the fluorine-based liquid, the proteins also are immune to contamination by microorganisms and enzymes.”

    Fluorochemicals are used in a range of applications, such as in making surfaces resistant to scratches and chemical degradation, as in the case of non-stick cookware.

    Eventually, Medina plans to study the use of fluorochemical coatings in other biological products, with the goal of eliminating the need to move any pharmaceutical via a cold chain.

    “This will allow access to medications in places where currently there is not,” Medina said. “For example, a soldier at war could be exposed to a harmful chemical agent. A fluorochemical-coated protein, which can be carried without refrigeration, could neutralize that agent immediately. This is part of DARPA’s interest in supplying this grant.”

    The grant is part of DARPA’s Young Faculty Award program, which provides funding, mentoring and networking opportunities to faculty early in their careers who plan to focus their research on Department of Defense and national security interests.

    In 2020, Medina published a study in ACS Nano on delivering therapeutic medications directly to a precise area of the body through an acoustically sensitive carrier, guided by ultrasound. The proposed DARPA-funded study is a spin-off of that study’s findings.

    “Janna Sloand, my former grad student who recently defended her doctoral research, came up with the coating technology in our last study,” Medina said. “It dovetails nicely with our new study, which will use those same coatings to take on the limitations of the cold chain.”

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    Source: https://bioengineer.org/1-million-grant-to-address-cold-storage-logistics-in-vaccine-delivery/

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    Reduced microbial stability linked to soil carbon loss in active layer under alpine permafrost degra

    Credit: NIEER Chinese researchers have recently discovered links between reduction in microbial stability and soil carbon loss in the active

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    Chinese researchers have recently discovered links between reduction in microbial stability and soil carbon loss in the active layer of degraded alpine permafrost on the Qinghai-Tibet Plateau (QTP).

    The researchers, headed by Prof. CHEN Shengyun from the Northwest Institute of Eco-Environment and Resources (NIEER) of the Chinese Academy of Sciences (CAS), and XUE Kai from University of Chinese Academy of Sciences, conducted a combined in-depth analysis of soil microbial communities and their co-occurrence networks in the active permafrost layer along an extensive gradient of permafrost degradation.

    The QTP encompasses the largest extent of high-altitude mountain permafrost in the world. This permafrost is different than high-latitude permafrost and stores massive soil carbon. An often ignored characteristic of permafrost is that the carbon pool in the active layer soil is more active and directly affected by climate change, compared to deeper layers.

    Triggered by climate warming, permafrost degradation may decrease soil carbon stability and induce massive carbon loss, thus leading to positive carbon-climate feedback. However, microbial-mediated mechanisms for carbon loss from the active layer soil in degraded permafrost still remain unclear.

    In this study, the researchers found that alpine permafrost degradation reduced the stability of active layer microbial communities as evidenced by increased sensitivity of microbial composition to environmental change, promoted destabilizing network properties and reduced resistance to node or edge attacking of the microbial network.

    They discovered that soil organic carbon loss in severely degraded permafrost is associated with increased microbial dissimilarity, thereby potentially contributing to a positive carbon feedback in alpine permafrost on the QTP.

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    The results were published in PNAS in an article entitled “Reduced microbial stability in the active layer is associated with carbon loss under alpine permafrost degradation”.

    This research was financially supported by the National Natural Science Foundation of China, the Strategic Priority Research Program (A) of CAS and the Second Tibetan Plateau Scientific Expedition and Research Program.

    Triggered by climate warming, permafrost degradation may decrease soil carbon stability and induce massive carbon loss, thus leading to positive carbon-climate feedback. However, microbial-mediated mechanisms for carbon loss from the active layer soil in degraded permafrost still remain unclear.

    Source: https://bioengineer.org/reduced-microbial-stability-linked-to-soil-carbon-loss-in-active-layer-under-alpine-permafrost-degra/

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    SNMMI Image of the Year: PET imaging measures cognitive impairment in COVID-19 patients

    Credit: G Blazhenets et al., Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of

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    Credit: G Blazhenets et al., Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg.

    Reston, VA–The effects of COVID-19 on the brain can be accurately measured with positron emission tomography (PET), according to research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2021 Annual Meeting. In the study, newly diagnosed COVID-19 patients, who required inpatient treatment and underwent PET brain scans, were found to have deficits in neuronal function and accompanying cognitive impairment, and in some, this impairment continued six months after their diagnosis. The detailed depiction of areas of cognitive impairment, neurological symptoms and comparison of impairment over a six-month time frame has been selected as SNMMI’s 2021 Image of the Year.

    Each year, SNMMI chooses an image that best exemplifies the most promising advances in the field of nuclear medicine and molecular imaging. The state-of-the-art technologies captured in these images demonstrate the capacity to improve patient care by detecting disease, aiding diagnosis, improving clinical confidence, and providing a means of selecting appropriate treatments. This year, the SNMMI Henry N. Wagner, Jr., Image of the Year was chosen from more than 1,280 abstracts submitted to the meeting and voted on by reviewers and the society leadership.

    “As the SARS-CoV-2 pandemic proceeds, it has become increasingly clear that neurocognitive long-term consequences occur not only in severe COVID-19 cases, but in mild and moderate cases as well. Neurocognitive deficits like impaired memory, disturbed concentration and cognitive problems may persist well beyond the acute phase of the disease,” said Ganna Blazhenets, PhD, a post-doctoral researcher in Medical Imaging at the University Medical Center Freiburg, in Freiburg, Germany.

    To study cognitive impairment associated with COVID-19, researchers carried out a prospective study on recently diagnosed COVID-19 patients who required inpatient treatment for non-neurological complaints. A cognitive assessment was performed, followed by imaging with 18F-FDG PET if at least two new neurological symptoms were present. By comparing COVID-19 patients to controls, the Freiburg group established a COVID-19-related covariance pattern of brain metabolism with most prominent decreases in cortical regions. Across patients, the expression of this pattern showed a very high correlation with the patients’ cognitive performance.

    Follow-up PET imaging was performed six months after the initial COVID-19 diagnosis. Imaging results showed a significant improvement in the neurocognitive deficits in most patients, accompanied by an almost complete normalization of the brain metabolism.

    “We can clearly state that a significant recovery of regional neuronal function and cognition occurs for most COVID-19 patients based on the results of this study. However, it is important to recognize the evidence of longer-lasting deficits in neuronal function and accompanying cognitive deficits is still measurable in some patients six months after manifestation of disease,” noted Blazhenets. “As a result, post-COVID-19 patients with persistent cognitive complaints should be presented to a neurologist and possibly allocated to cognitive rehabilitation programs.”

    “18F-FDG PET is an established biomarker of neuronal function and neuronal injury,” stated SNMMI’s Scientific Program Committee chair, Umar Mahmood, MD, PhD. “As shown the Image of the Year, it can be applied to unravel neuronal correlates of the cognitive decline in patients after COVID-19. Since 18F-FDG PET is widely available, it may therefore aid in the diagnostic work-up and follow-up in patients with persistent cognitive impairment after COVID-19.”

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    Abstract 41. “Altered regional cerebral function and its association with cognitive impairment in COVID 19: A prospective FDG PET study.” Ganna Blazhenets, Johannes Thurow, Lars Frings and Philipp Meyer, Department of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Nils Schroeter, Tobias Bormann, Cornelius Weiller, Andrea Dressing and Jonas Hosp; Department of Neurology and Clinical Neuroscience, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; and Dirk Wagner, Department of Internal Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

    All 2021 SNMMI Annual Meeting abstracts can be found online at https://jnm.snmjournals.org/content/62/supplement_1.

    About the Society of Nuclear Medicine and Molecular Imaging

    The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging, vital elements of precision medicine that allow diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.

    SNMMI’s members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit http://www.snmmi.org.

    “As the SARS-CoV-2 pandemic proceeds, it has become increasingly clear that neurocognitive long-term consequences occur not only in severe COVID-19 cases, but in mild and moderate cases as well. Neurocognitive deficits like impaired memory, disturbed concentration and cognitive problems may persist well beyond the acute phase of the disease,” said Ganna Blazhenets, PhD, a post-doctoral researcher in Medical Imaging at the University Medical Center Freiburg, in Freiburg, Germany.

    Source: https://bioengineer.org/snmmi-image-of-the-year-pet-imaging-measures-cognitive-impairment-in-covid-19-patients/

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