PHILADELPHIA -– A study at the University of Pennsylvania School of Veterinary Medicine has identified the function of one of the earliest antibodies in the animal kingdom, an ancient immunoglobulin that helps explain the evolution of human intestinal immune responses. It was discovered to play a predominant role in the guts of fish and paves the way for a better understanding of human gut immunity as well as for safer, healthier approaches to keeping fish from pathogen infections. The findings appear in the online version of Nature Immunology and will be featured on the cover of the September issue.
The study identified unique aspects of the structure and function of a fish antibody, IgT, and points to this molecule as the most ancient vertebrate immunoglobulin specialized in mucosal immunity. The findings challenge the present paradigm that specialization of immunoglobulin isotypes into different body areas, i.e., intestine and blood, arose during the evolution of four-legged creatures, or tetrapods. While IgT was discovered five years ago, its structure and function remained an enigma.
In addition to characterizing the protein structure of IgT, the study provides direct evidence for the existence of a novel B cell lineage uniquely producing IgT. In the gut, IgT+ B cells represent the predominant B cell subset. More critically, the study showed that responses of rainbow trout IgT to an intestinal parasite were only detected in the gut, whereas IgM responses were confined to plasma. Supporting further the role of IgT in mucosal immunity, the researchers found that a majority of trout intestinal bacteria were coated with IgT. The research team concluded that the specialization of immunoglobulin isotypes into different body compartments is a universal feature of all jawed vertebrate immune systems, a feature required for health maintenance in environmentally different exposed body areas that require different immune needs.
“Immunoglobulins like IgA, IgX and the newly discovered IgT are evolutionarily distant,” said Oriol Sunyer, associate professor in the Department of Pathobiology at Penn Vet. “Their specialization into mucosal compartments must have occurred independently by a process of convergent evolution driven by similar selective pressures operating on the gut environment of fish, amphibians and mammals.”
Significantly, the study shows that fish IgT and human IgA systems appear to utilize similar solutions to maintain healthy intestines, therefore Sunyer indicated that “future studies on IgT will further unravel structural and functional aspects of human mucosal immunoglobulins that are key to their role in keeping our intestines free of pathogens.”
With aquaculture being the fastest growing animal food sector in the United States, as well as in the global marketplace, the findings should also impact fish health and vaccinology. In that regard, all prior studies carried out in teleost fish during the last few decades have missed the specific contribution of IgT in protecting fish from pathogens. Sunyer’s studies establish that teleost fish contain not one, as originally believed, but at least two functional immunoglobulins, IgM and IgT, that respond to pathogenic challenge in different body areas. Thus, the new capability of measuring not only IgM but also IgT responses will greatly facilitate the evaluation and understanding of fish immune responses as well as the protective effects of fish vaccines.
“The design of future fish vaccines is likely to be more effective, stimulating not only systemic but also mucosal immunity as we are now able to measure IgT-induced responses,” Sunyer said.
“Dr. Sunyer’s work will change how we look at disease prevention in fish, and his breakthrough will have a profound impact on the future of the aquaculture industry,” said Roger Beachy, director of the National Institute of Food and Agriculture. “I am proud that the USDA supports such innovative research.”
Immunoglobulins first emerged in vertebrates around 400 million years ago along with the appearance of the jawed fish, the most ancient living vertebrate species with jaws. Throughout evolutionary time, immunoglobulins diversified into several isotypes with specialized roles in innate and adaptive immunity in different parts of the body, according to the study’s author, who says the study of immunoglobulins from fish and other animal species will continue providing new insights that are fundamental for understanding the role of these molecules in protecting us against pathogens.
The research was funded by the National Science Foundation, the National Institutes of Health and the United States Department of Agriculture.
PHILADELPHIA — Femida Handy, a professor in the University of Pennsylvania School of Social Policy & Practice, has been appointed editor-in-chief of Nonprofit and Voluntary Sector Quarterly, the peer-reviewed academic journal of non-profit and philanthropic studies, by the Association for Research on NonProfit Organizations and Voluntary Action, ARNOVA.
Handy researches micro-foundational issues in the economics of the non-profit sector and volunteerism as well as issues of social accounting.
“Nonprofit and Voluntary Sector Quarterly is the premier academic vehicle to highlight innovation in the nonprofit and non-governmental organization sector,” Eric Ashton, the associate director of the School of Social Policy & Practice’s NonProfit/NGO Leadership Program, said. “Dr. Handy brings considerable academic rigor and international research experience to this position. She will accelerate the journal to the next level of excellence.”
The journal places an emphasis on interdisciplinary collaboration, provides cutting-edge research and analysis and focuses on public policy, organization and leadership, philanthropy, voluntarism and civil society.
Other School of Social Policy & Practice contributors include the associate dean for research and president of ARNOVA, Ram Cnaan, who is a member of the publication’s editorial board, along with Michael Shier and Itay Greenspan, Ph.D. students who will serve as its managing editors.
PHILADELPHIA –- The Positive Psychology Center of the University of Pennsylvania and the John Templeton Foundation have announced the recipients of the 2010 Templeton Positive Neuroscience Awards, $2.9 million given to 15 new research projects at the intersection of neuroscience and positive psychology.
The winning projects explore a range of topics including how the brain enables humans to flourish, the biological bases of altruism and the effects of positive interventions on the brain.
“Research has shown that positive emotions and interventions can bolster health, achievement and resilience and can buffer against depression and anxiety,” said Martin E. P. Seligman, director of the Penn Positive Psychology Center. “And while considerable research in neuroscience has focused on disease, dysfunction and the harmful effects of stress and trauma, very little is known about the neural mechanisms of human flourishing. Creating this network of positive neuroscience researchers will change that.”
The 15 winning proposals represent 24 researchers and were selected from 190 submissions. The Awards identify the winning researchers as future leaders in the new field of positive neuroscience.
The Positive Neuroscience Project was established in 2008 by Seligman with a $5.8 million grant from the John Templeton Foundation. Seligman founded the quickly growing field of Positive Psychology in 1998 based on the idea that what is good in life is as worthy of scientific study as what is disabling in life.
Winners were selected by the Positive Neuroscience Steering Committee, comprised of psychologists, neuroscientists and fellow researchers from Stony Brook University, Harvard University, the University of Colorado, the John Templeton Foundation, Emory University, Ohio State University and Penn.
Winning studies include: • Abigail Marsh, assistant professor of psychology at Georgetown University, will receive $180,000 to study neural functioning of heroically altruistic people, such as those who donate a kidney to save the life of a stranger. Marsh has shown that sensitivity to others’ fearful facial expressions predicts altruism better than gender, mood, self-reported empathy or general sensitivity. • James K. Rilling, associate professor of anthropology, psychiatry and behavioral sciences at Emory, and Richmond R. Thompson, associate professor of psychology and neuroscience at Bowdoin College, will receive $200,000 to study why some fathers are better parents than others. Children with nurturing and playful fathers are more likely to be popular with peers and teachers, be fair and generous and have higher IQs than kids with absent fathers. • Kateri McRae and Iris Mauss, assistant professors of psychology at the University of Denver, will receive $180,000 to study the neural bases of resilience. Extreme stress cripples some people, while others bounce back and some even thrive due to post traumatic growth. Research shows that positive emotions and flexible thinking are hallmarks of resilience and can be developed through training and therapy. • Elena Antonova from King’s College London has received $180,000 to study how meditation affects sensory processing in the brain. Human brains filter the barrage of information flowing into our bodies through our senses. We wouldn’t be able to notice anything if we noticed everything, so our brains help us quickly habituate to repeated signals, filtering most information under the radar of attention. Experienced meditators do not habituate to stimuli like most of us, nor do people with schizophrenia. • Alon Chen and Elad Schneidman from Weizmann Institute of Science will receive $200,000 to study the warm glow of companionship at the molecular level. Positive social interactions make us happier and healthier and even buffer us against ailments including heart disease and depression. • Britta Hölzel and Mohammed Milad from Harvard Medical School will use $200,000 to find out if meditation helps people conquer their fears. Mindfulness meditation impacts the structure and function of the ventromedial prefrontal cortex, hippocampus and amygdala, brain regions that are also part of the neural circuits critical for deactivating conditioned fears. • Psyche Loui from Harvard Medical School was awarded $180,000 to study how the brain enables artistic genius. Loui will study neural connectivity in musicians with absolute pitch and people with synesthesia to better understand supernormal perception. • Jason Mitchell and Jamil Zaki from Harvard will study the relationship between doing good and feeling good and how both can be amplified within and between people. Sharing happiness may double your pleasure. • India Morrison from the University of Gothenburg will study how pleasurable touch affects the way we understand and relate to others. Touch is more than skin deep because skin is a social and emotional organ. Touch carries affective meaning, enhances social bonding and shapes our beliefs about what it feels like to be in another person’s skin. Morrison will focus on a recently discovered type of nerve fiber that transmits the pleasure of gentle touch, and she will examine a people with a rare genetic mutation resulting in a severe reduction of those nerve fibers. • Stephanie D. Preston from the University of Michigan and Tony W. Buchanan from St. Louis University will study the neural differences between sensing that someone is in pain or danger and taking action to help them. Empathy is bodily response. Research shows that, when people feel another’s pain psychologically, they also resonate physically in heart rate, facial muscles, skin response, neural activity and pupil dilation. Even so, people frequently fail to help those in need and sometimes even cause their distress. • Laurie Santos from Yale University will investigate how altruism evolved in the brain. Positive Psychology research has shown that good deeds lead to great pleasure. Altruistic actions can increase happiness even more than beneficial but selfish actions. Santos will work with two primate species, rhesus macaques and capuchin monkeys, to find out if they also experience prosocial actions as inherently rewarding. • William Cunningham from Ohio State University and Alexander Todorov from Princeton University will study how people’s social goals influence how their brain processes important social stimuli. • Tor Wager and Sona Dimidjian from the University of Colorado will study how compassionate thinking impacts brain function and leads to more caring behavior. The researchers will conduct a four-week compassion meditation training and identify neural processes that support positive thoughts and affiliation with others. • Thalia Wheatley from Dartmouth College will study how different brain regions process emotion and support social intelligence. People see emotion in movement and hear emotion in music. She will study how different neural regions work together to process complex but universally understood emotion and how that relates to empathy and social skill. • Adam Anderson from the University of Toronto will study the neural and genetic bases of positivity and resilience. Anderson will examine how specific genes influence dopamine-related brain functions and behaviors and how that supports positive emotion, creative problem solving and recovery.
Additional information about the Positive Neuroscience Project and Templeton Positive Neuroscience Awards is at www.posneuroscience.org.
Gene for Cholesterol and Cardiovascular Disease Identified through Genome Scan
Wednesday, August 4, 2010
Researchers at the University of Pennsylvania School of Medicine, the Broad Institute, Massachusetts General Hospital, and Alnylam Pharmaceuticals Inc., are some of the first to prove that a gene linked to a disease trait by genome wide association studies (GWAS) can be clinically relevant and an important determinant of disease risk.
PHILADELPHIA –- The “Unmentionable World of Human Waste” will get more than just mentioned when Rose George’s “The Big Necessity: The Unmentionable World of Human Waste and Why It Matters” takes its place as the text for the 2010-11 Penn Reading Project at the University of Pennsylvania.
On Sept. 5, incoming students will join with faculty leaders to discuss the book as the first University activity centered around the Year of Water, an academic theme that involves multidisciplinary activities across Penn’s 12 schools and several resource centers, including Penn Museum, Earth and Environmental Sciences and Civic House, as well as outside organizations such as the Philadelphia Global Water Initiative. Year of Water programming will feature lectures and symposiums with scholars in the field, conferences, site visits and more.
In “The Big Necessity,” the author, a Penn alumna, addresses one of the few remaining taboos: human waste disposal. The book discusses differing cultural practices while also revealing the global health problem of sanitation and the need to provide people with functioning toilets.
In her book, George points out that disease spread by bodily waste kills more people worldwide every year than any other single cause of death. Questions of environmental sustainability surface as well, as toilets are responsible for the single largest use of water in American homes.
The Penn Reading Project, now in its 20th year, was created as an introduction for incoming freshmen to academic life at Penn. Other recent reading projects have focused on Neil Shubin’s “Your Inner Fish,” Michael Pollan’s “The Omnivore’s Dilemma,” and Benjamin Franklin’s “Autobiography,” as well as on Thomas Eakins’s painting “The Gross Clinic.”
PHILADELPHIA — Marsha I. Lester and Gary Molander of the University of Pennsylvania have been named 2010 fellows of The American Chemical Society, an honor bestowed on 192 scientists who have demonstrated outstanding accomplishments in chemistry and made important contributions to ACS, the world’s largest scientific society.
Marsha I. Lester is the Edmund J. Kahn Distinguished Professor at Penn and a physical chemist whose research combines theoretical approaches with new experimental techniques. She is editor of the Journal of Chemical Physics, and her laboratory’s most recent work obtained the first high-resolution spectrum of peroxynitrous acid, a key intermediate in atmospheric chemistry.
Gary A. Molander is the Hirschmann-Makineni Professor of Chemistry and an organic chemist whose research involves the development of new synthetic methods and their application to the synthesis of organic molecules. Within this context, new ways to form carbon-carbon bonds selectively are being explored utilizing novel reagents as well as organometallic catalysts.
“Whether it’s making new materials, finding cures for disease or developing energy alternatives, these Fellows are scientific leaders, improving our lives through the transforming power of chemistry,” ACS President Joseph S. Francisco said. “They are also consummate volunteers who contribute tirelessly to the community and the profession.”
The Fellows program began in 2009 to recognize and honor ACS members for achievements in and contributions to science, the profession and the Society. This year’s group, like the first 163 Fellows named in 2009, represents academe, industry and government.
The 2010 Fellows will be recognized on Aug. 23 during the Society’s national meeting in Boston.
On the heels of the enactment of the Wall Street Reform and Consumer Protection Act, the University of Pennsylvania's Wharton School announces that Treasury Deputy Secretary Neal S. Wolin - one of the Administration's key architects of financial reform - will speak to students, faculty and business leaders. Deputy Secretary Wolin will deliver remarks on the path forward for the implementation of these historic reforms and engage in a question and answer dialogue with the audience.
Thursday, August 5, 2010, 3:30 p.m.
The Dhirubhai Ambani Auditorium The Wharton School of the University of Pennsylvania Jon M. Huntsman Hall 3730 Walnut Street Philadelphia, PA 19104
PHILADELPHIA –- Bioengineers at the University of Pennsylvania have created a system to control the flexibility of the substrate surfaces on which cells are grown without changing the surface properties, providing a technique for more controlled lab experiments on cellular mechanobiology, an important step in the scientific effort to understand how cells sense and respond to mechanical forces in their environment.
Researchers created a library of micromolded, hexagonally spaced elastomeric micropost arrays, one to a few microns high, on which they cultivated cells. The micropost system allowed engineers to modulate the rigidity and flexibility of the substrate surface without changing the adhesive or other material surface properties that could affect cell growth. Post height determined the degree to which a post would bend in response to a cell’s horizontal traction force. The system enabled researchers to map cell traction forces to individ¬ual focal adhesions and spatially quantify sub-cellular distributions of focal-adhesion area, traction force and focal-adhesion stress.
The research, published in the current issue of the journal Nature Methods, demonstrated that the height of the posts determined the flexibility of the surface substrate, which in turn impacted the cell’s morphology, leading to differences in focal adhesions, cytoskeletal contractility and stem-cell differentiation. Furthermore, early changes in cytoskeletal contractility measured by the devices predicted lineage fate decisions made days later by the stem cells.
“The library of micro¬post arrays spanned a more than 1,000-fold range of rigidity from 1.31 nN μm−1 up to 1,556 nN μm−1,” said Chris Chen, lead author and the Skirkanich Professor of Innovation in Bioengineering in the School of Engineering and Applied Science at Penn. “Furthermore, the micropost array library will be made available to researchers in other laboratories.”
Using current methods, it was not possible to change surface rigidity without also affecting other cellular properties such as the amount of active ligand molecules presented to cells, making it difficult to tease out the precise contributions of rigidity to cellular behavior.
Prior techniques employed the culture of cells on hydrogels derived from natural extracellular matrix proteins at different densities; however, changing densities of the gels impacted not only mechanical rigidity but also the amount of the binding or signaling ligand, leaving uncertainty as to the relevant contribution of these two matrix properties on the observed cellular response. Other synthetic hydrogels have been used that can vary rigidity without altering ligand density, but such systems cannot separate whether cells are sensing flexibility of individual molecules or of the macroscale mechanics.
“Although hydrogels will continue to be important in characterizing and controlling cell-material interactions, alternative approaches are necessary to understand how cells sense changes in substrate rigidity,” Chen said.
In the body, cells do not exist in isolation but are in constant contact with other cells and with the extracellular matrix, providing structural support as well as both molecular and mechanical signals. In prior research, Chen’s team has demonstrated that the push and pull of cellular forces drives the buckling, extension and contraction of cells during tissue development. These processes ultimately shape the architecture of tissues and play an important role in coordinating cell signaling, gene expression and behavior, and they are essential for wound healing and tissue homeostasis in adult organisms.
This study was conducted by Chen, Jianping Fu, Yang-Kao Wang, Michael T. Yang, Ravi A. Desai, Xiang Yu and Zhijun Liu of the Department of Bioengineering at Penn. Fu and Wang are now faculty members at the University of Michigan and the Skeletal-Joint Research Center of the National Cheng-Kung University Medical School.
The research was funded by grants from the National Institutes of Health, the National Science Foundation, the Army Research Office Multidisciplinary University Research Initiative, the Material Research Science and Engineering Center, the Institute for Regenerative Medicine, Penn’s Nano/Bio Interface Center, the Center for Musculoskeletal Disorders of the University of Pennsylvania, the New Jersey Center for Biomaterials and the American Heart Association.