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Roses are red and so is . . . blood?

Thu, 2019-02-14 08:55

When you think of blood, chances are you think of the color red. But blood actually comes in a variety of colors, including red, blue, green, and purple. This rainbow of colors can be traced to the protein molecules that carry oxygen in the blood. Different proteins produce different colors.

Red Blood

Humans, along with most other animals, birds, reptiles, and fish, have red blood. We all use an oxygen-carrying blood protein, known as hemoglobin, that contains iron. It’s the iron that gives blood its dark red color in the body.  When blood comes into contact with air, it turns the classic scarlet red. Some people appear to have blue blood in their veins. That’s just an optical illusion caused by the way the skin filters light.

Blue Blood

The term blue blood often refers to people related to kings and queens. But organisms with actual blue-colored blood are far from royal. They include snails, spiders, slugs, octopuses, and squid. The protein that carries oxygen in these creatures is called hemocyanin. Instead of iron, this protein contains copper. The blood appears clear when it’s not carrying oxygen. It turns blue when it picks up oxygen.

Green Blood

Science fiction aliens aren’t the only ones with green blood. Earthbound creatures with green blood include fantastically shaped sea worms, some leeches, and earthworms. These animals have a blood protein called chlorocruorin. It’s similar to hemoglobin but doesn’t hold oxygen as tightly. Also, it floats free in the bloodstream instead of being inside a blood cell.

Purple Blood

Peanut worms, duck leeches, and bristle worms, all of which live in the ocean, use the protein hemerythrin to carry oxygen in the blood. Without oxygen, their blood is clear in color. When it carries oxygen, it turns purple.

NIGMS Grantees Receive National STEM Mentoring Award

Wed, 2019-01-30 08:55

In a previous post, we highlighted two NIGMS-funded winners of the 2018 Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM ). For January’s National Mentoring Month, we tell you about other awardees: J.K. Haynes, Virginia Shepherd, and Maria da Graça H. Vicente.

J. K. Haynes, Ph.D., Morehouse College

J. K. Haynes, Ph.D., Morehouse College. Credit: Morehouse College.

During his long scientific career, J. K. Haynes has been a successful researcher and served in prestigious administrative and national leadership positions. But he is most proud of the individual lives he has impacted. Teaching and mentoring are his passions.

During his four decades at Morehouse College—the nation’s only private, historically black, liberal arts college for men—Haynes has influenced the lives of more than 3,000 African American undergraduates. He inspired many of these young men to pursue graduate degrees in STEM  fields. He has also mentored many junior faculty and others at Morehouse.

Key to Haynes’s mentorship philosophy is instilling a sense of professionalism, integrity, compassion, and competence. To empower mentees to overcome obstacles, he helps them develop a healthy outlook on uncertainty and rejection. He also emphasizes interdisciplinary studies and intercultural experiences, and the importance of networking and embracing new ideas.

Morehouse students at work in the research laboratory of Dr. Jeffrey Handy, assistant professor of biology at Morehouse and one of Dr. Haynes’ mentees. Credit: Morehouse College.

During his time at Morehouse, Haynes served as director of the Office of Health Professions, director of the honors program, chair of the department of biology, dean of the division of science and mathematics, and faculty member of the NIGMS-supported Institutional Research and Academic Career Development Awards (IRACDA) collaboration between Emory University and Morehouse. He has also served on advisory committees and as a board member  for several national and government science organizations.

In 2015, Haynes received a Champion of Change at HBCUs Award from the Whitehouse. His biography is included in the 1996 book Distinguished African American Scientists of the 20th Century, and an interview with him  is included in the History Makers Digital Oral Archive (2011).

Virginia Shepherd, Ph.D., Vanderbilt University

Virginia Shepherd, Ph.D., Vanderbilt University. Credit: Vanderbilt University.

For more than 25 years, Virginia Shepherd has championed science and math education in public schools. Her interest in this area was initially sparked by a talk she attended in 1992, in which scientists were encouraged to spend 4 hours per week in a K–12 science classroom. Since that time, she has continued to seek new ways of improving STEM  education in schools and promoting professional development for K–12 science teachers.

A professor emerita of education at Vanderbilt’s Peabody College, Shepherd founded and directed the university’s Center for Science Outreach (CSO),  which connects scientists with the K–12 community, both locally in Nashville, Tennessee, and nationally. The CSO’s School for Science and Math at Vanderbilt (SSMV),  funded in part by the Science Education Partnership Award, is a joint venture between Vanderbilt and Metropolitan Nashville Public Schools. Twenty-six students from each high school class year participate in a 4-year, research-centered experience 1 day per week on the Vanderbilt campus. They start with classroom instruction from professors and progress to completing individual research projects. Similarly, the Day of Discovery program provides middle school students with an immersive, research-based STEM curriculum 1 day per week at a magnet high school. Among SSMV students, 86 percent have gone on to college to major in a STEM field or graduate with a STEM major. Fifty-five percent of SSMV students are female.

Shepherd looks over the shoulder of a student participating in the School for Science and Math at Vanderbilt. Credit: Vanderbilt University.

Shepherd also started the Scientist in the Classroom  program, now in its 19th year. The program is a collaboration between Nashville’s public schools and five local higher-learning institutions, including Vanderbilt. It creates partnerships between science teaching fellows (STFs) and public-school science teachers in elementary and middle schools. The STFs, about 40 percent of whom represent underrepresented populations are graduate or post-graduate students who work with teachers to develop hands-on, inquiry-based activities and provide classroom demonstrations. The STFs also help tutor students and direct student research projects. About 10 percent of the STFs have gone on to become K–12 teachers. The program benefits some 130 graduate and undergraduate students, 110 K–12 teachers, and more than 10,000 K–12 students.

Along with her Presidential Award, Shepherd has received many accolades related to her dedication to promoting STEM education, including the Mayor’s Award for Outstanding Partner in 2011 and the Mary Jane Werthan award for contributions to the advancement of women in 2008.

Maria da Graça H. Vicente, Ph.D., Louisiana State University

Maria da Graça H. Vicente, Ph.D., Louisiana State University. Credit: LSU IMSD.

Maria da Graça H. Vicente  is both a distinguished professor of chemistry and an influential scientific mentor. Dozens of her mentees now hold scientific leadership positions in universities, government, and industry. Vicente’s impact is especially strong among students from groups that are underrepresented in STEM  disciplines.

Since 2007, Vicente has directed the Initiative for Maximizing Student Development (IMSD) at Louisiana State University (LSU). This NIGMS-supported program provides research training and career development to graduate students across the country. Its long-term goal is to produce a diverse pool of well-trained biomedical scientists.

As director of LSU’s IMSD program, Vicente and her staff arrange meaningful research experiences, training activities, educational mentoring plans, and networking opportunities for participating students. She believes that keys to the success of the program include providing students with resources to explore career options, access to a strong network of collaborations, and support for making critical career and personal decisions.

Dr. Vicente with IMSD scholars (from the left: Paris Taylor, Briasha Jones, Ashley Merriweather, Dr. Vicente, Tanner Reed, Amy Turner) at the LSU 2018 Summer Undergraduate Research Forum. Credit: LSU IMSD.

Under Vicente’s leadership, LSU’s IMSD program expanded the university’s outreach to underrepresented students. The program also increased student retention and graduation rates and boosted students’ competitiveness for entering the next phase of their educational and professional lives. In part due to her efforts, more African Americans receive doctorate degrees in chemistry from LSU than from anywhere else in the nation. The program even strengthened LSU’s faculty publication record and competitiveness for research awards.

Along with her Presidential Award, Vicente has received numerous other teaching and mentoring awards

How Three Physician Scientists Are Taking Strides to Improve Our Health

Wed, 2019-01-09 10:00

Brain injuries, cancer, infections, and wound healing are some of the complex and pressing
health concerns we face today. Understanding the basic science behind these diseases and biological processes is the key to developing new treatments and improving patient outcomes. Physician scientists—medical doctors who also conduct laboratory research—are essential to turning knowledge gained in the lab into innovative treatments, surgical advances, and new diagnostic tools.

In this blog, we highlight the work and impact of three trauma surgeon scientists funded by NIGMS at different stages in their careers: Dr. Nicole Gibran (current grantee), Dr. Rebecca Minter (former grantee), and Dr. Carrie Sims (former grantee). Their work, despite the historical underrepresentation of women in the physician scientist training community, has led to revolutionary surgical treatments, new therapeutics, better screening, and improved quality of life for patients.

Dr. Nicole Gibran: Transforming Burn Recovery

Dr. Nicole Gibran, director of University of Washington’s Regional Burn Center at Harborview and University of Washington’s David and Nancy Auth-Washington Research Foundation Endowed Chair for Restorative Burn Surgery. Credit: University of Washington Medicine.

Dr. Nicole Gibran  has built an impressive career treating burn victims and helping them regain their function, strength, mobility, and quality of life. As the director of the University of Washington’s Regional Burn Center at Harborview,  which treats more than 900 burn patients each year, Gibran splits her time between patient care and researching the biological processes that drive wound healing and repair.

Scientists still don’t fully understand how the body repairs wounds, and clinicians are unsure how to treat wounds more effectively while reducing scarring. Gibran tries to address these knowledge gaps in her lab. Her work focuses on understanding the mechanisms of wound repair, especially how nerves contribute to inflammation and scarring. Nerves in the skin trigger the release of proteins at different stages of the inflammation response after a burn injury, and Gibran’s lab has identified key proteins and receptors that signal scar formation at the injury site. Understanding why, how, and when scars form after burns could help scientists develop better burn treatments that preserve tissue function, maximize recovery, and reduce scarring.

Gibran demonstrates a unique ability and commitment in bringing together people of different backgrounds and experiences. For example, she convinced the scientific burn community to include patients among every working group at all state-of-the-science symposia, regardless of the topic. As a result, researchers now see and hear from patients as they discuss everything from nutrition to future treatment directions. She believes that researchers and clinicians “need to find more opportunities to hear the patient’s voice” so they better understand their gaps in knowledge.

Severe burns are traumatic injuries that damage not only the skin and surrounding tissues, but also the mind. Burn patients can be left with deformities and scarring that affect how the public views them and how they navigate the world. Gibran hopes to change that. She advocates for increased public awareness of burn injuries  and ensures that all patients treated at the University of Washington Burn Center have access to psychological services early in their care. Gibran’s devotion to her patients’ physical and psychological recovery is a key reason why the burn center is a valuable and esteemed resource for the Washington state community.

To those looking to replicate her incredibly successful funding history and launch their own research careers, Gibran has some advice:

  • Don’t be shy about reaching out to people who could be mentors and counsel you.
  • Learn how to say “no.”
  • Have a good research story to tell.
  • Understand why your research is truly important and how it will directly help patients have better outcomes.
  • Have a good working relationship with your program director.
  • Get creative with finding funding sources.

*Gibran received her initial grant as a young investigator through NIGMS’ now phased-out FIRST (First Independent Research Support and Transition) award. Since then, Gibran has received many R01 grants through NIGMS.

Dr. Rebecca Minter: Rethinking Surgical Training

Dr. Rebecca Minter, chair of the Department of Surgery at the University of Wisconsin–Madison. Credit: UW Department of Surgery. Credit: Andy Manis.

Dr. Rebecca Minter  is always looking to improve her patients’ quality of life and to develop a more effective surgical training paradigm. An internationally recognized pancreaticobiliary surgeon who specializes in early detection and treatment of pancreatic diseases, she has successfully launched a pancreatic diseases prevention program. Also a leader in surgical education, Minter is the newly appointed A.R. Curreri Professor and chair of the Department of Surgery at the University of Wisconsin (UW)–Madison.

With her impressive resume, people would never know that Minter entered residency with no idea of what an academic surgeon was. She points to NIGMS as pivotal in her choice of following this path and in laying a solid foundation for her extraordinary career. She says that NIGMS training support exposed her to the excitement of taking part in moving the field forward. “And it taught me how to write grants and secure funding and how to ask the right questions,” Minter adds.

Although her surgical training and career development as a mentored trainee were exceptional, Minter recognizes that this isn’t every fellow’s experience. She notes that her success wouldn’t be the same if NIGMS hadn’t made those investments in her future as an early-career investigator and credits her mentor, Lyle Moldawer, Ph.D., with launching her career. Given her appreciation for the mentoring she received, it’s no surprise that she’s interested in the impact of investments in trainees and the significance of career development, and is researching how to train the next generation of surgeons more effectively

At UW-Madison, Minter devotes her time to supporting the surgical faculty and researching how to improve training programs in surgery to ensure all graduating surgeons are competent and prepared for independent practice. The training approach historically has focused on the number of procedures a surgical resident has performed and years of training rather than a resident’s ability, which better predicts independence at the conclusion of the program. Focusing primarily on procedural numbers as a key measure of success also tells little about the quality of training the residents have received learning that technique.  Did they obtain leadership opportunities? What level of independence did they have performing the procedure? How hands-on were the attending physicians?

Minter challenges her colleagues to broaden their definition of effective surgical training by having all graduating trainees care for a family member upon graduation. This requires significant and innovative approaches to both resident and faculty development—innovations that Minter and her colleagues are developing.

*Minter, received both an NIGMS T32 National Research Service Award Institutional Postdoctoral Training Grant and a Mentored Clinical Scientist Development Award at the beginning of her medical training and faculty career.

Dr. Carrie Sims: Advocating for Change

Dr. Carrie Sims, associate professor of surgery and attending surgeon at the hospital of the University of Pennsylvania, and research director of the Division of Traumatology, Surgical Critical Care and Emergency Surgery, at the University of Pennsylvania School of Medicine. Credit: University of Pennsylvania Perelman School of Medicine. Credit: University of Pennsylvania.

As a trauma surgeon in Philadelphia, Dr. Carrie Sims  sees it all—from gunshot wounds and brain injuries to internal bleeding and shock. She is highly skilled at quickly diagnosing and treating the many life-threatening injuries that confront her in the operating room at the University of Pennsylvania School of Medicine and the Presbyterian Medical Center of Philadelphia. But Sims is not just a trauma surgeon. Sims has made it her mission to understand and address the root causes of two kinds of trauma that impact our communities: gun violence and intimate partner violence, often referred to as domestic violence.

Because Sims treats numerous gunshot wounds in Philadelphia every year, she decided to research factors that may be contributing to this huge public health problem. She teamed up with a colleague from the University of Pennsylvania Injury Science Center  to study the epidemiology of gun violence in the community. They analyzed police statistics for firearm injuries and found that race appears to play a critical role in increasing someone’s risk of a firearm injury.  She now advocates for increased research into this and other racial disparities related to public health.

Domestic violence is another leading cause of injury Sims is called on to treat. Based on her research, Sims implemented a mandatory educational program on domestic violence at the Trauma Center at Penn for all trauma residents. Studies commissioned by the Department of Health and Human Services show that mandatory screening can increase domestic violence detection and lead to more successful interventions and injury prevention. Sims continues to monitor and improve the screening program’s effectiveness and encourages the medical community to address domestic violence nationally.

*Sims received an NIGMS Mentored Clinical Scientist Development Award in 2011.

Festive Flu Virus Structure

Thu, 2018-12-20 08:50

Credit: Rommie Amaro, Jacob Durrant, Adam Gardner, and colleagues.

Ah, December—a month suffused with light-filled holidays, presents, parties . . . and the spread of colds and flu. This playful image uses a festive approach to the serious science of understanding and finding ways to combat the flu virus.

The structure shows the H1N1 influenza (flu) virus, so named for the hemagglutinin (H) and neuraminidase (N) molecules shown in ice blue on the surface of the virus. Also appearing in atomic-level detail is the virus’ outer envelope (white), matrix proteins (bright green), and genetic material (ribonucleoproteins in red, pink, and dark green).

Extreme Healing, Weird Genomics, and Bloodsucking Invaders

Wed, 2018-12-12 08:40

Quick quiz:  Which organism . . .

  • Can regrow a severed spinal cord?
  • Is a culinary delicacy overseas but an invasive pest in the U.S.?
  • Reveals insights about tissue regeneration, evolution, and cancer biology?

Give up? It’s the sea lamprey.

A direct descendant of one of the first organisms to develop a backbone, these remarkable creatures are considered “living fossils.” Best of all, they can regrow a severed spinal cord—a feat we humans can only dream about. Credit: Jeramiah Smith, University of Kentucky.

This leechlike creature has several unusual—and enviable—characteristics that make it an ideal research organism for a variety of scientific investigations.

Lampreys can do something no human has ever accomplished: repair a damaged spinal cord. Humans with spinal cord injuries are often paralyzed and lose bowel and bladder control. Lampreys, in contrast, can recover fully, even after their spinal cords are sliced clean through. Within 12 weeks, they’re swimming and functioning normally.

Genetically speaking, lampreys are also highly unusual. Most animals guard their genomes zealously, since altering a single letter of DNA code could cause a devastating genetic disease or set the stage for cancer. Lampreys, meanwhile, toss out 20 percent of their DNA while still embryos. The process is called programmed genome rearrangement (PGR). Some researchers suspect that it might help protect lampreys from cancer.

How can throwing away hundreds—or even thousands—of genes help prevent cancer? Here’s the thinking: All animals have genes used only during very early embryonic development, long before they develop tissues and organs. Most animals permanently switch off (“silence”) these genes once they no longer need them. Unfortunately, due to cellular errors, silenced genes can occasionally be switched back on. Reactivating certain silenced genes can contribute to developing cancer.

Rather than merely silencing unnecessary genes, lampreys permanently dispose of them. By doing so, they eliminate the risk of reactivating genes that could lead to cancer.

Sea lamprey is eaten as a delicacy in several European and Asian countries. But in the Great Lakes, it’s an invasive, parasitic, bloodsucking predator that has decimated native trout populations. Credit: Wikimedia Commons, U.S. Environmental Protection Agency.

As a result of PGR, lampreys have two genomes. Their complete genome contains 99 pairs of chromosomes and is found only in eggs and sperm. The other genome, a slimmed-down, post-PGR version, is found in all other cells of the lamprey’s body.

Lampreys sit on an unusual branch of the evolutionary tree. Called jawless fish, they split off more than 500 million years ago from other vertebrates (the group of animals that includes mammals, bony fish, birds, and reptiles). Because they’re ancient members of the vertebrate family, lampreys can help scientists understand which genes and traits are essential to all vertebrates. The creatures also highlight which cellular processes—such as spinal cord regeneration and PGR—were lost during the evolution of most of the vertebrates. These lessons can provide new insights into the genetic rules of our own species.

CRISPR Illustrated

Thu, 2018-11-29 16:36

You’ve probably heard news stories and other talk about CRISPR. If you’re not a scientist—well, even if you are—it can seem a bit complex. Here’s a brief recap of what it’s all about.

In 1987, scientists noticed weird, repeating sequences of DNA in bacteria. In 2002, the abbreviation CRISPR was coined to describe the genetic oddity. By 2006, it was clear that bacteria use CRISPR to defend themselves against viruses. By 2012, scientists realized that they could modify the bacterial strategy to create a gene-editing tool. Since then, CRISPR has been used in countless laboratory studies to understand basic biology and to study whether it’s possible to correct faulty genes that cause disease. Here’s an illustration of how the technique works.

How the CRISPR System Works

The CRISPR system has two components joined together: a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence) and a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA).

Once inside a cell, the CRISPR system locates the DNA it is programmed to find. The CRISPR seeking device recognizes and binds to the target DNA (circled, black).

The Cas9 enzyme cuts both strands of the DNA.

Researchers can insert into the cell new sections of DNA. The cell automatically incorporates the new DNA into the gap when it repairs the broken DNA.

CRISPR has many possible uses, including:

  • Insert a new gene so the organism produces useful medicines.
  • Help treat genetic diseases.
  • Create tailor-made organisms to study human diseases.
  • Help produce replacements for damaged or diseased tissues and organs.

Surgeon Chris McCulloh Stands Up to Disability

Thu, 2018-11-15 10:43

Credit: Chris McCulloh. Chris McCulloh

Job: 4th-year general surgical resident, Morristown Medical Center in New Jersey
Grew up in: Manhattan
When not at work, he’s: Programming, coding, thinking about artificial intelligence, and machine learning
Hobbies: Writing/producing electronic music, weightlifting

Ten years ago, Chris McCulloh planned to enter medical school and fulfill his dream of becoming a surgeon. Instead, just months before he was to start med school, he ended up a patient. A freak accident—slipping on a hardwood floor, flying backwards, and landing neck-first on the edge of a glass coffee table—left him with both legs paralyzed at age 28. Undaunted, he deferred entering medical school for a year, undergoing surgery and spending months in rehab.

McCulloh prepares for surgery while “20/20” host Elizabeth Vargas stands alongside him as part of a 2017 interview.
Credit: Morristown Medical Center.

McCulloh has since finished medical school and recently completed a 2-year pediatric surgery research fellowship at Nationwide Children’s Hospital in Columbus, Ohio. He is now two-thirds of the way through his surgical residency at the Morristown (New Jersey) Medical Center, thanks to the assistance of a specialized wheelchair that allows him to stand nearly to his 6-foot-3 height and helps him perform five to six surgeries a day.

He’s received plenty of attention for being a surgeon with a disability. Along with several print media stories, he was interviewed in 2013 for CBS’ “The Doctors,” and in 2017, ABC’s “20/20” included McCulloh in an episode on physicians with disabilities. But it’s not the wheelchair that distinguishes McCulloh, says Gail Besner, a pediatric surgeon and researcher who hired McCulloh as a postdoctoral fellow. Rather, it’s his enthusiasm, natural research skills, and exceptional surgical prowess that make him special. Besner sees no reason why he won’t reach his goal of landing a highly competitive pediatric surgical residency. “I think he’s capable of doing anything he puts his mind to,” she says.

Pursuing a Dream

After the 2008 accident that left him paralyzed, McCulloh didn’t know how he would ever be able to perform surgery. But he found encouragement from the rehab physicians he worked with at Mount Sinai Hospital in New York City, as well as from several disabled physicians he met who had managed to succeed even before the 1990 Americans with Disabilities Act. He had never been one to back down from a challenge, so he headed to Case Western Reserve School of Medicine in Cleveland, Ohio, one of the schools that had accepted him before his accident. A plastic surgeon in Hawaii who also uses a wheelchair provided guidance to McCulloh about what he would need to do to become a surgeon, including finding and funding a standing wheelchair.

At Case Western, an encounter with a neurologist who worked with children inspired McCulloh to shadow a pediatric surgeon during his surgery rotation. By the end of that month, he had found his passion: performing life-saving surgery on children. It meant overcoming immense physical challenges and competing in one of the most sought-after specialties in medicine, but it was a dream he was determined to pursue.

Testing Treatments for Necrotizing Enterocolitis (NEC)

Although squeezing in 2 years of postdoctoral research alongside a veteran pediatric surgeon isn’t a mandatory part of the road to pediatric surgery, 80 to 85 percent of those who successfully earn a surgery residency take that path.

That’s how McCulloh found his way to longtime NIGMS grantee Besner, despite having no prior research experience. After Besner hired him, she discovered that McCulloh qualified for an NIGMS disability supplement. The grant kickstarted McCulloh’s research and allowed him to attend conferences where he could network and present his award-winning findings.

Besner’s lab focuses on necrotizing enterocolitis (NEC), a disease that attacks the bowel and is a leading cause of death for premature infants. McCulloh chose to pursue findings from Besner’s lab suggesting that stem cells may protect against NEC. Using a NEC rat model, McCulloh tested whether certain types of stem cells were more effective than others. Four looked promising: mesenchymal stem cells derived from amniotic fluid and from bone marrow, and neural stem cells derived from amniotic fluid and from the neonatal gut.

However, using stem cells in premature babies raises potential problems, which include stimulating tumor growth. McCulloh examined whether he could get a similar effect using a product secreted by stem cells. He studied exosomes—messenger particles that leave the cell that created them and enter other cells. McCulloh separated exosomes from the various types of stem cells and injected them into NEC-afflicted rats. He discovered that exosomes were just as effective as stem cells against NEC. Besner’s lab also tracked their progress to see where they ended up and found exosomes in highest concentrations in damaged tissue, giving even more weight to the idea that they support healing.

“These findings support the potential for a noncell-based therapy for NEC in the future,” says Besner.

As for McCulloh, though he’s still passionate about surgery, he’s discovered a new outlet in Besner’s lab. “I find myself looking at problems I encounter clinically and thinking about how I could do a study to solve them,” he says. “My plan right now is to get through my residency and a pediatric fellowship, but then there’s a good chance I’ll start up my own lab. It feeds a need I have to find solutions to problems.”

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