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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

    Sex differences in COVID-19 outcomes

    Credit: Mary Ann Liebert, Inc., publishers In a study of more than 10,600 adult patients hospitalized with COVID-19, women had

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    In a study of more than 10,600 adult patients hospitalized with COVID-19, women had significantly lower odds than men of in-hospital mortality. They also had fewer admissions to the intensive care unit and less need for mechanical ventilation. Women also had significantly lower odds of major adverse events, including acute cardiac injury, acute kidney injury, and venous thromboembolism, according to an article in the peer-reviewed Journal of Women’s Health. Click here to read the article now.

    “This comprehensive analysis is the largest study to date that directly assesses the impact of sex on COVID-19 outcomes,” stated Rachel-Maria Brown, MD, Zucker School of Medicine at Hofstra/Northwell, and coauthors. “Our study strongly demonstrates female sex to be associated with lower odds of in-hospital outcomes, major adverse effects and all-cause mortality as compared to male sex after controlling for confounding variables.” The authors propose some of the protective factors that may contribute to these findings.

    In the accompanying editorial entitled “Lessons Learned from COVID-19 Sex Disparities,” Annabelle Santos Volgman, MD, Rush University Medical Center, and coauthors, suggest various mechanisms by which female sex may confer a protective advantage against COVID-19 infection. One advantage may be the extra X chromosome, which carries multiple genes responsible for innate and adaptive immunity.

    Volgman and coauthors emphasize that “although women have less mortality risk with COVID-19, we need to exercise caution not to send a message to deliver subpar care to women with COVID-19 or decrease measures to prevent their infection. Our evolving knowledge should not reduce attention paid to women admitted for COVID-19.”

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    Research reported in this publication was supported by the National Institutes of Health under Award Number R24AG064191, R01LM012836, R01 NR018443. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    About the Journal

    Journal of Women’s Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women’s Health, Richmond, VA, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women’s healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women’s Health website. Journal of Women’s Health is the official journal of the Society for Women’s Health Research.

    About the Publisher

    Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. A complete list of the

    Source: https://bioengineer.org/sex-differences-in-covid-19-outcomes/

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    UTHSC awarded $1.5 million HRSA grant for sexual assault nurse examiner training

    Credit: UTHSC Memphis, Tenn. (June 16, 2021) – The University of Tennessee Health Science Center’s College of Nursing has received

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    Memphis, Tenn. (June 16, 2021) – The University of Tennessee Health Science Center’s College of Nursing has received a three-year, $1.5 million grant from the Department of Health and Human Services Health Resources and Services Administration (HRSA) to fund a much-needed expansion of Sexual Assault Nurse Examiner (SANE) training and certification in West Tennessee.

    SANE programs are designed to train nurses to address survivors’ needs and provide trauma-informed care. The 21 counties of West Tennessee have only five certified SANE nurses, four of whom practice in Shelby County. But the Tennessee Bureau of Investigation received nearly 1,600 reports of sexual assault in West Tennessee in 2019, indicating a significant shortage of nurses certified to meet the need for this care.

    Andrea Sebastian, DNP, PNP, SANE-P, an assistant professor in the UTHSC College of Nursing, has worked as a child abuse nurse practitioner for the last seven years at Le Bonheur Children’s Hospital and will serve as project manager of the SANE Training and Education through Partnerships for Underserved Populations (STEP UP) grant.

    “During this time, I have recognized the importance of SANE nurses in our community. Currently, we do not have enough SANE nurses in West Tennessee to provide exams and resources to victims,” Dr. Sebastian said. “With this grant, we will be able to increase access to these invaluable resources and help victims of sexual assault in our community.”

    The UTHSC team will work with West Tennessee Healthcare, the Shelby County Crime Victims and Rape Crisis Center, and the Whiteville Family Medical Clinic on the project. The team’s goal is to transform the nursing workforce by increasing the supply, distribution, and retention of certified SANEs and improving access to timely, expert care for all sexual assault survivors in West Tennessee.

    Assistant Professor Christie Manasco, PhD, RN, is one of the co-investigators on the grant. “The funding from this grant will significantly help us close the gaps to equitable SANE care in West Tennessee. The efforts supported by these funds will help us to reduce inequalities and disparities and promote better outcomes for survivors,” she said.

    Beginning in July, the STEP UP grant team will launch a plan to recruit up to 61 registered nurses or advanced practice registered nurses (APRNs) from the West Tennessee counties, with a focus on the rural and underserved areas. The grant will pay for participants to earn certifications through community or academic programs for adult and pediatric patients, known as SANE-A® and SANE-P®.

    The grant team will also work with regional stakeholders to develop and implement a regional Sexual Assault Response and Resource Team (SARRT) that will assess the needs for sexual assault services in the area, reduce barriers to SANE training, and coordinate SANE clinical training opportunities. Grant funding also will be used to develop and provide resources for SANE self-care, peer mentoring, continuing education, and recertification.

    Dr. Sebastian will be supported on this grant by co-investigators including Dr. Manasco, Assistant Professor Lisa Beasley, DNP, APRN, NP-C, RN; Assistant Professor Sally Humphrey, DNP, ARN, CPNP-PC; and Assistant Professor Diana Dedmon, DNP, FNP-BC, director of Clinical Affairs. College of Nursing Dean Wendy Likes, PhD, DNSc, APRN-Bc, FAANP, will serve as women’s health adviser on the grant, and the program coordinator for the Doctor of Nursing Practice DNP program, Trimika Bowdre, PhD, MPH, will be the evaluation adviser.

    “The College of Nursing is very grateful for the funding to support this important work of providing appropriate care to this very vulnerable group of people,” Dr. Likes said. “The need for this in West Tennessee is beyond question. I personally look forward to working with this team in the College of Nursing and our community partners to provide this vital service to our communities.”

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    As Tennessee’s only public, statewide, academic health system, the mission of the University of Tennessee Health Science Center is to bring the benefits of the health sciences to the achievement and maintenance of human health through education, research, clinical care, and public service, with a focus on the citizens of Tennessee and the region. The main campus in Memphis includes six colleges: Dentistry, Graduate Health Sciences, Health Professions, Medicine, Nursing and Pharmacy. UTHSC also educates and trains medicine, pharmacy, and/or health professions students, as well as medical residents and fellows, at major sites in Knoxville, Chattanooga and Nashville. For more information, visit http://www.uthsc.edu. Find us on Facebook: facebook.com/uthsc, on Twitter: twitter.com/uthsc and on Instagram: instagram.com/uthsc.

    Source: https://bioengineer.org/uthsc-awarded-1-5-million-hrsa-grant-for-sexual-assault-nurse-examiner-training/

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    Pioneering chemistry approach could lead to more robust soft electronics

    Credit: Udit Chakraborty, Cornell University RESEARCH TRIANGLE PARK, N.C. — A new approach to studying conjugated polymers made it possible

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    RESEARCH TRIANGLE PARK, N.C. — A new approach to studying conjugated polymers made it possible for an Army-funded research team to measure, for the first time, the individual molecules’ mechanical and kinetic properties during polymerization reaction. The insights gained could lead to more flexible and robust soft electronic materials, such as health monitors and soft robotics.

    Conjugated polymers are essentially clusters of molecules strung along a backbone that can conduct electrons and absorb light. This makes them a perfect fit for creating soft optoelectronics, such as wearable electronic devices; however, as flexible as they are, these polymers are difficult to study in bulk because they aggregate and fall out from solution.

    “Conjugated polymers are a fascinating class of materials due to their inherent optical and electronic properties which are dictated by their polymer structure,” said Dr. Dawanne Poree, program manager, U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. “These materials are highly relevant to a number of applications of interest to Army and DoD including portable electronics, wearable devices, sensors, and optical communication systems. To date, unfortunately, it has been difficult to develop conjugated polymers for targeted applications due to a lack of viable tools to study and correlate their structure-property relationships.”

    With Army funding, researchers at Cornell University employed an approach they pioneered on other synthetic polymers, called magnetic tweezers, that allowed them to stretch and twist individual molecules of the conjugated polymer polyacetylene. The research was published in the journal Chem.

    “Through the use of novel single-molecule manipulation and imaging approaches, this work provided the first observations of single-chain behaviors in conjugated polymers which lays the foundation for the rational design and processing of these materials to enable widespread application,” Poree said.

    Previous efforts to address the solubility of conjugated polymers have often relied upon chemical derivatization, in which the structures are modified with functional groups of atoms. However, that approach can affect the polymer’s innate properties.

    “The conjugated polymer is really a prototype,” said Dr. Peng Chen, the Peter J.W. Debye professor of chemistry and chemical biology at Cornell. “You always modify it to tailor it for applications. We are hoping everything we measured – the fundamental properties of synthesis kinetics, the mechanical property – become benchmark numbers for people to think about other polymers of the same category.”

    In 2017, Chen’s group was the first to use the magnetic tweezers measurement technique to study living polymerization, visualizing it at the single-molecule level. The technique had already been used in the biophysics field for studying DNA and proteins, but no one had successfully extended it to the realm of synthetic polymers.

    The process works by affixing one end of a polymer strand to a glass coverslip and the other end to a tiny magnetic particle. The researchers then use a magnetic field to manipulate the conjugated polymer, stretching or twisting it, and measuring the response of a single polymer chain that grows.

    The amounts are so small, they stay soluble in solution, the way bulk amounts normally would not.

    The team measured how long chains of conjugated polymers, which consist of hundreds of thousands of monomer units, grow in real time. They discovered these polymers add a new monomer per second, a much faster growth than their nonconjugated analogs.

    “We found that while growing in real time, this polymer forms conformational entanglements,” Chen said. “All polymers we have studied form conformational entanglements, but for this conjugated polymer this conformational entanglement is looser, allowing it to grow faster.”

    By pulling and stretching individual conjugated polymers, so-called force extension measurements, the researchers were able to assess their rigidity and better understand how they can bend in different directions while remaining conjugated and retaining electron conductivity.

    They also discovered the polymers displayed diverse mechanical behaviors from one individual chain to the next-behaviors that had been predicted by theory but never observed experimentally.

    The findings highlight both the uniqueness of conjugated polymers for a range of applications as well as the strength of using a single-molecule manipulation and imaging technique on synthetic materials.

    “Now we have a new way to study how these conjugated polymers are made chemically and what is the fundamental mechanical property of this type of material,” Chen said. “We can study how these fundamental properties change when you start tailoring them for application purposes. Maybe you can make it more mechanically flexible and make the polymer longer, or adjust the synthesis condition to either synthesize the polymer in a faster or slower way.”

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    Visit the laboratory’s Media Center to discover more Army science and technology stories

    As the Army’s national research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command’s core technical competencies, we lead in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation’s wars and come home safely. DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. DEVCOM is a major subordinate command of the Army Futures Command.

    Source: https://bioengineer.org/pioneering-chemistry-approach-could-lead-to-more-robust-soft-electronics/

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