Neuroscience Is a Modern Tradition at Amherst College – Collegenews.org

AMHERST, Mass., Nov.13, 2006(AScribe Newswire) The number of undergraduate college students taking up neuroscience is large and growing, according to the Association of Neuroscience Departments and Programs (ANDP), which estimates that 5,000 people now graduate every year with a major in this academically demanding and intellectually exciting field. The first recorded use of the word neuroscience to mean comprising the sciences of brain and behavior was in Nature in 1970, the same year the Society for Neuroscience was founded. With extraordinary speed, Amherst College became the first institution in the United States to offer an undergraduate major in the new science, in 1973, at a time when miracles such as targeted medication for clinical depression or brain implants to alleviate human blindness were the stuff of science fiction.

At that time Stephen George, now the Manwell Family Professor in Life Sciences (Biology and Neuroscience), was brought to Amherst as an assistant professor of biology to work in the neuroscience program. To understand the nervous system, he said then, you have to understand its function on all levels. Thirty years later, hes still asking these questions: How does the mind work? How can we explain the behavior of animals and people? What goes wrong when someone is mentally ill or emotionally disturbed? Neuroscience is the modern attempt to answer these questions through the study of the brain-and in 2006 we enjoy a vastly greater physical understanding of the brain.

James Olds, a 1978 graduate of Amherst, and the director of the Krasnow Institute for Advanced Study and Krasnow University Professor of Computational Neuroscience at George Mason University, describes the changes in neuroscience. Our animal model in 1973 was the rat, he says of laboratory research into the human brain. In 2006, its the college sophomore.

Neuroscience at Amherst grew out of the biophysics major of the 50s and 60s, which produced some distinguished neuroscientists, in a field that had not yet been named. In 1970 the Alfred P. Sloan Foundation decided to support the new field of neuroscience at all levels. A proposal for an undergraduate program in neuroscience from Amherst received $400,000. The program first offered a neuroscience major in 1973. Undergraduate neuroscience programs are now quite common, as shown by the active Faculty for Undergraduate Neuroscience group associated with the Society for Neuroscience. Stephen George was among the founders of this organization, and Sarah M. Turgeon, an associate professor of psychology at Amherst, has served on its executive council.

The ANDP notes in its most recent annual report that the existence of undergraduate programs in neuroscience is a relatively recent phenomenon. The ANDP counts 33 undergraduate program members, but only two programs were founded before 1980, six programs between 1980 and 1989 and the rest only after 1989.

Perhaps because of its origin in biophysics, neuroscience at Amherst College is a demanding discipline. One student guide noted wryly that neuro is the major to avoid if you want to take the country-club approach to college. Yet many choose it. Almost from the beginning the neuroscience department has attracted a dozen or more majors in every class. Mirroring the national trend, the numbers are growing.

Several fields of science, including biology, chemistry, psychology, mathematics, computer science and physics, are important in studying the nervous system, and Amherst students who major in neuroscience take courses in all of these fields. The courses include laboratory work emphasizing modern techniques, such as recording electrical activity from single nerve cells, measuring behavioral effects of drugs and working with proteins and nucleic acids. The neuroscience major consists of 14 courses, more courses than required for any other major at Amherst. Neuroscience majors also take part in the Neuroscience Seminar, in which Amherst students and faculty discuss current research and through which guest neuroscientists visit to lecture on their work. This fall, the seminar heard a 1980 Amherst graduate, Neal Swerdlow of the UCSD Medical School, discuss Neuropsychiatric Disorders of Impaired Central Inhibition: Things Weve Learned in the Blink of an Eye.

Neuroscience at Amherst offers senior students opportunities for honors thesis research projects. Usually based in the research areas of the neuroscience faculty, these projects have delved into the neurophysiology of the visual system, control of neural excitability, developmental psychobiology, animal models of schizophrenia and the neural basis of feeding behavior.

Amherst students have frequently been able to present the results of their research at the national meetings of the Society for Neuroscience or the Biophysical Society. For example, Tiffany Lin, a 2006 graduate, recently received a competitive Travel Award from the Faculty for Undergraduate Neuroscience, which took her to Atlanta for the annual meeting of the Society for Neuroscience. Lins presentation, Repeated exposure to PCP alters stress-induced behavior and striatal c-Fos, described the results of her research as an undergraduate working with Turgeon in the psychology department.

Lin is now at the behavioral genetics laboratory at the Mailman Research Institute at McLean Hospital in Boston, where shes working on the mechanisms of neurogenesis. Most Amherst neuroscience majors enter graduate or professional programs, either right after graduation or after working or traveling for a time. Their careers may involve medicine, research, teaching or a combination of these. They are doing research in laboratories at the National Institutes of Health, teaching high school in Boston, practicing medicine around the country or working in the business world in a biomedical field. They all maintain their keen fascination with how the brain works, sharpened by the rigors of neuroscience at Amherst College.

CONTACTS: Stephen George, Amherst College, 413-542-2477

James Olds 78, George Mason University, 703-993-4378

Tiffany Lin 06, McLean Hospital, 617-855-2009

Sarah Turgeon, Amherst College, 413-542-2625

Paul Statt, Amherst College Media Relations, 413-542-8417

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Applying neuroscience to Cannes-winning work: Airbnb’s Until We All Belong – AdNews

'Until We All Belong' marks the most public corporate declaration for marriage equality in Australia to date.

AdNews has partnered with Neuro-Insight to bring an analysis of some of this year's winning Cannes work to understand what it is that made them successful through a neuroscience lens.

Companies have begun taking a serious stance on same-sex marriage. While the Australian government is yet to make a decision, brands are definitely rallying the cause. Following the launch of Airbnb'sUntil We All Belong, which centres on a unfinished ring that symbolises the gap in marriage equality, the analysts and Neuro-Insight wanted to find out what the public think about the initiative.

Airbnb - Until We All Belong

Clemenger BBDO have had a stellar year at Cannes taking out the coveted Agency of the Year award in conjunction with winning a grand total of 56 Lions across a number of different categories. Amongst that silverware, Clemenger picked up a silver lion in the Media category & a bronze lion in Design category for the marriage equality themed campaign they produced for the online booking service, Airbnb. Featuring several different people, firstly describing what appears to be a broken black ring, who then broach the issue of marriage equality, the spot adds a human element to what has, at least in this country, become a highly politicised and divisive public debate. There is no denying that this is a very powerful and emotive piece of storytelling that Clemenger has created, but what measurable impact does this spot leave with the viewer? As part of our exclusive Cannes on the Brain series, now in its sixth year, we analysed the brain activity of typical viewers to understand the impact that Clemengers creativity had on the brain.

How we did it

Neuro-Insight measured brain activity to see how 50 females and 50 males respond to the ad. The specific technology used by Neuro-Insight is founded in work originally developed for academic and neuroscience research, and has been used to analyse the effectiveness of Cannes award winners for over four years. The technology allows us to simultaneously record viewers second-by-second changes in approach (like)/withdraw (dislike), emotional intensity, engagement and memory whilst watching advertisements. The measure Neuro-Insight predominantly focusses on, is based on its strong and highly researched link in influencing consumer behaviours is long-term memory encoding. This measure reveals what the brain is storing (or encoding) into conscious and unconscious long-term memory. Neuro-Insights Memory Encoding graph reveals how elements of the ad are stored in long-term memory. The higher the graph, the more strongly that moment in the ad is stored in memory and the more likely it will influence consumer behaviour

Time Series

Below are the times series graphs for both male and female viewers responses to the Airbnb commercial. The red trace reflects memory encoding from the left hemisphere, which is primarily responsible for the encoding of the detail in experiences, such as text or dialogue. In contrast, the right hemisphere which is reflected by the blue line is concerned with the storing of global features, such as soundtracks, scenery, facial expressions as well as the emotional underpinnings of a particular experience.

Long term memory encoding for Female Viewers

Long term memory encoding for Male Viewers

The creative starts by featuring several different people who attempt to describe the symbolism of a broken ring. As the narrative flows from one talent to the next, we start to see differences emerge between male and female viewers, the most notable of which occurs the average level of memory encoding itself. During this narrative sequence, the level of memory encoding in female viewers is much higher than that of male viewers and closely tracks each new talent and their personal description of what a broken ring symbolises. In contrast, the response of male viewers is reduced, sitting largely within the moderate range of brain activity and does not show any initial preference for talent or message. It is not until the narrative links the missing gap in the ring as missing acceptance that we see a sharp retrigger in memory encoding for male viewers, which results in following visuals of the couple and their message of a disconnect being very strongly encoded.

The second half of the advertisement also follows a similar trend, with female viewers continuing to elicit generally higher levels of memory encoding to each new talent and their personal stories. However, our data does reveal that both genders responded strongly to key message of the gap needing to be closed. In females, this is met with an exceptionally high memory encoding response, whereas in male viewers, although not as strongly encoded, the response did retrigger and drive an increase in memory encoding. As the narrative transitions into the personal pledges and notwithstanding the lower memory encoding response in male viewers, the levels of engagement and emotional intensity increased, indicating that the narrative was eliciting a strong emotional impact in both groups. This contrasted with the first half of the advertisement, where the levels of engagement and emotion experienced by both groups was lower.

In the lead up to final branding, we see a brief interval of Conceptual Closure that effects the Until we all belong tagline screen in both genders. Conceptual Closure occurs when the brain perceives an event boundary, such as a narrative sequence has coming to an end and takes a brief period to process and store the previous experience. In this case, it is the combination of shortened pledges and fading soundtrack which is likely to have driven this effect. Importantly, the introduction of a voiceover call to action was powerful enough to retrigger and sustain memory encoding through to final branding in both genders.

In summary, Clemengers advertisement is a powerful piece of creative storytelling, that elicits different responses in male and female viewers alike. Female viewers stay with the entire piece, strongly encoding the personal journeys and brand message. In contrast, male viewers tend to encode the most pertinent message points rather than the general narrative. Therefore, if any cut-downs were produced, it would be recommended to consider using the specific talent and messaging that spoke to missing acceptance and closing the gap as these two scenes were either very strongly encoded or triggered a strong memory encoding response in both genders. In all, the main contention of the advertisement is well encoded within the URL call to action and final branding frame, which we feel, also makes this a very effective piece of advertising.

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Stress testhow scientists can measure how animals are feeling – Phys.Org

July 10, 2017 Credit: University of Western Sydney

To help determine how stress is affecting animals across Australia, researchers at Western Sydney University are utilising non-invasive methods to help farmers, zookeepers and pet owners ensure their animals are happy and healthy.

Stress is an important biological response for animals as it helps their bodies prepare to fight or flee from danger. But many animals in the modern world are forced to coexist with humans in farms, zoos or homes, and the onset of chronic stress can have devastating results, both for them and their owners.

"Stress can affect the weight of farm animals, leading to losses for animal producers, and can disrupt the breeding patterns of endangered animals in captivity," says Dr Edward Narayan, Senior Lecturer in Animal Science, from the School of Science and Health.

"Here at Western Sydney University we are working with clients to collect animal scats under routine husbandry and run them through our laboratories to measure stress levels."

When a stress result is sparked in an animal, the brain-body starts to release biomolecules such as cortisol, which is the main stress hormone in large animals such as humans, elephants and sheep. Ultimately, this cortisol is broken up by the kidneys, and ends up in excreta.

"By testing these scats, we can monitor and track animals from a distance and gain a snapshot and new understanding of their mood and health," says Dr Narayan.

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This research comes under the umbrella of conservation physiology, a rapidly expanding field of study that measures the physiological responses of organisms subject to human interference. While the traditional field of conservation biology seeks to manage the natural environment to help protect threatened species, conservation physiology is a way to improve the health and happiness of animals in contact with humans.

For animals, a life with minimal stress is linked to happiness, as high stress reflects fear and anxiety. In most cases, happiness for animals revolves around the daily needs for survival, such as securing food and shelter. By reducing stress among animals, scientists can help them redirect energy often used for survival to other uses, such as increasing fat reserves and reproduction.

"Considering human activity has pushed the world to the sixth mass extinction event, measuring the stress levels of native animals may help conserve their dwindling numbers by providing real-time data on species' physiological resilience and vulnerabilities towards anthropogenic induced environmental changes. By having access to this data, researchers are able to help direct conservation and management efforts towards at-risk species," says Dr Narayan.

The potential applications are vast, as the studies can be replicated across species living in different settings, from koalas in nature parks, to sheep in pasture, and even domestic animals in apartments. It also enables researchers to monitor population health during management interventions, such as species translocation and invasive pest species eradication programs.

"At the moment, we're working with sheep farmers in regional Australia to help monitor the physiological markers of their animals, with the ultimate aim of tracking their mood. By ensuring the sheep are stress free, we can improve their productivity in terms of meat quality and reproduction. In addition, we're also working with international animal rescue programs such as Animals Asia to provide crucial data on the stress physiology of Asiatic black bears being rescued from bile farms in Vietnam."

In addition to analysing scats, Dr Narayan and researchers at Western Sydney University also examine other samples, such as hairs and urine. The researchers are planning to utilise drone technology to help farmers in remote locations track their animals as they are moved across vast distances. The tests can even be ordered by domestic animal owners looking to track the stress responses of their pets.

"Cats and dogs are very prevalent in Australia, and are obviously affected by human behaviour. For example, a dog may be stressed if it's not provided with tender loving care, or a cat may be upset if it's not able to access a warm space in winter. What the non-invasive tests can measure is their stress responses over time, giving us baseline indicators of their mood and allowing us to intervene if necessary by pinpointing the moments of great stress in their lives, and working backwards to discover the cause."

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India lags in clinical research field: Dr Mishra – Times of India

Nagpur: Even as the health care system has seen rapid advancements over the years, the country has witnessed minuscule progress in the field of research in physiology. This is evident from the fact that in the year 2014-15, total 43,689 publications came out from all 421 medical colleges of the country, including eight premier institutions. The contribution of the department of physiology was, however, just 0.82%.

Revealing these figures, chancellor of Krishna Institute of Medical Sciences Deemed University, Dr Ved Prakash Mishra, rued the fact that the field of physiology hasn't grown much in the country.

Mishra also talked about the poor research work being carried out in private clinics. "If we talk about our country's private clinical set-ups, the conversion of their clinical work into research material is mere 4.2%, while in a small country like Poland their utilization is 92%. In the US, their utilization rate is 72%, while even China manages it to an extent of 52%."

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India lags in clinical research field: Dr Mishra - Times of India

EMCC practical nursing students graduate – Meridian Star

Thirteen students graduated from East Mississippi Community Colleges Practical Nursing program in a ceremony Thursday night in the Lyceum Auditorium on the Golden Triangle campus. Wendy T. Gullett was presented with the Florence Nightingale Award, which is awarded to the student who most embodies the spirit of nursing. The Practical Nursing program is a 12-month course of study designed to prepare students to become licensed practical nurses. Students are taught nursing skills, nutrition, anatomy and physiology, human growth and development, pharmacology, maternal child nursing, emotional and mental illness, and medical/surgical nursing. In addition to the Florence Nightingale Award, three students received Clinical Excellence Awards for exceeding the expectations of their instructors. Those studentsare:Lea Chaffin, JaylinNealand Joy Veazey. The 2017 graduates of EMCCs Practical Nursing program are: Lea Chaffin of Hamilton;TamariaB. Clay of Brooksville; Wendy T. Gullett of Starkville; Luke Hodges of Cleveland; Kathryn Kisner of West Point; Chelsea Latham of Eupora; Jaylin N. Neal of Columbus; Edwin Phillips of Starkville; Joy Veazey of Columbus: Melanie Wallace of Amory;AlyscaWebb of Senatobia; Lauren Wilson of Columbus; and Breanna Yeatman of Starkville.

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EMCC practical nursing students graduate - Meridian Star

Nanoscale forces measured in aortic smooth muscle cells tell story … – Phys.Org

July 10, 2017 Nanonet Force Microscropy (NFM) can measure the contractile inside-out forces of a single cell attached to multiple fibers. Shown here are f-actin (red), paxillin (green), and the nucleus (blue). Scale bar = 20 micron. Credit: Abinash Padhi, STEP Lab, Virginia Tech

Researchers from Virginia Tech and the University of Pittsburgh have collaborated to employ a novel nanoscale fibrous system that can measure the tiny forces exerted by and upon individual cells with extreme precision. The team hopes that this platform, which investigators call nanonet force microscopy (NFM), will provide new knowledge about smooth muscle cell biology that could have implications for treating cardiovascular disease, which is still a leading cause of death in the United States.

The results of investigations on cells using this platform appear in the "Forces" issue of the journal Molecular Biology of the Cell, in the article "Nanonet Force Microscopy for Measuring Forces in Single Smooth Muscle Cells of Human Aorta," published July 7, 2017.

The main goal of this current study, said Julie Phillippi, assistant professor at the University of Pittsburgh Department of Cardiothoracic Surgery whose laboratory provided healthy human patient smooth muscle cells for the study, was to quantify forces that healthy cells experience in various conditions of stress. The fibrous nanonet itself was designed in the mechanical engineering laboratory of Amrinder Nain, associate professor at Virginia Tech and member of the American Society for Cell Biology. Forces measured using NFM, Nain said, include forces exerted by the cells themselves and forces exerted by the environment on the cells. "Everything in nature exerts and experiences a physical force," said Nain. "This platform measures both simultaneously."

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Phillippi said that previous work tested the mechanical strength of whole aortic tissue and understanding the single cell biomechanics is vitally important. Single-cell studies provide insight into the proteins involved in the fleeting so-called focal adhesions that most cells make as they move around their microenvironment. The NFM assembly aims to mimic, in as physiologically relevant a way as possible, what cells endure within the collagen fibers of the extracellular matrix (ECM)the matrix that supports cell growth in living things. Tweaking the artificial matrix by changing fiber diameter, density, and spacing in a controlled and repeatable manner, as well as using cells from diseased patients at different disease severities, will allow Phillippi and Nain to simulate the conditions experienced by cells in many realistic situations.

"We have looked very closely at how the collagen and elastin fibers in the ECM are arranged and the micro-architecture and everything points to these microstructural defects in the ECM contributing to the weakening of the aortic walls and the ballooning of the vessel," said Phillippi. "What we don't know is, are these ECM proteins arranged that way from birth or is it something that happens over time? Or is it both? What role do the cells play? This engineered platform will allow us to answer some of those questions." Furthermore, Nain said, NFM could reveal the heterogeneity of cells taken from the same patient or from different patients with the same disease state down to the single-cell resolution.

Next steps for Phillippi and Nain include testing cells from the Pittsburgh team's large repository of aortic specimens from patients, collected in collaboration with Thomas Gleason, Chief of the Division of Cardiac Surgery, University of Pittsburgh, to establish a database of baseline forces for many types of cells that researchers and clinicians can use to diagnose and treat disease. "The platform gives us the ability to create in vitro disease models with multiple layers of sophistication," said Phillippi.

In a broader context, the ability to achieve precise control on fiber diameter, spacing, and orientation to mimic native fibrous environments, will allow NFM to interrogate the push and pulls in a cell's journey in developmental, disease, and repair biology.

Explore further: Cancer cells 'talk' to their environment, and it talks back

More information: Alexander Hall et al. Nanonet force microscopy for measuring forces in single smooth muscle cells of the human aorta, Molecular Biology of the Cell (2017). DOI: 10.1091/mbc.E17-01-0053

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Houston team one step closer to growing capillaries – Phys.Org

July 10, 2017 by Jade Boyd Researchers from Rice University and Baylor College of Medicine have shown they initiate a process called tubulogenesis that is crucial to the formation of blood-transporting capillaries. In microscopic images taken a different times during a weeklong experiment, researchers tracked the changes in cells (green) and cell nuclei (orange) using fluorescent markers. Credit: Jeff Fitlow/Rice University

In their work toward 3-D printing transplantable tissues and organs, bioengineers and scientists from Rice University and Baylor College of Medicine have demonstrated a key step on the path to generate implantable tissues with functioning capillaries.

In a paper published online in the journal Biomaterials Science, a team from the laboratories of Rice bioengineer Jordan Miller and Baylor College of Medicine biophysicist Mary Dickinson showed how to use a combination of human endothelial cells and mesenchymal stem cells to initiate a process called tubulogenesis that is crucial to the formation of blood-transporting capillaries.

The work is an important step with fragile endothelial cells (ECs) made from "induced pluripotent stem cells," or iPSCs, a type of cell that can potentially be made from the cells of any human patient. Because iPSCs can be patient-specific, researchers hope to find ways of using them to generate tissues and replacement organs that can be transplanted without risk of rejection by a patient's immune system. But the fragility of endothelial cells during laboratory growth has limited the utilization of this critical cell type, which is found in all vasculature.

"Our work has important therapeutic implications because we demonstrate utilization of human cells and the ability to live-monitor their tubulogenesis potential as they form primitive vessel networks," said study lead author Gisele Calderon, a graduate student in Miller's Physiologic Systems Engineering and Advanced Materials Laboratory.

"We've confirmed that these cells have the capacity to form capillary-like structures, both in a natural material called fibrin and in a semisynthetic material called gelatin methacrylate, or GelMA," Calderon said. "The GelMA finding is particularly interesting because it is something we can readily 3-D print for future tissue-engineering applications."

Tissue engineering, also known as regenerative medicine, is a field aimed at integrating advances in stem cell biology and materials science to grow transplantable replacement tissues and organs. While tissue engineers have found dozens of ways to coax stems cells into forming specific kinds of cells and tissues, they still cannot grow tissues with vasculaturecapillaries and the larger blood vessels that can supply the tissues with life-giving blood. Without vascularization, tissues more than a few millimeters in thickness will die due to lack of nutrients, so finding a way to grow tissues with blood vessels is one of the most sought-after advances in the field.

Miller, who earned his Ph.D. at Rice in 2008, has studied vascularization in tissue engineering for more than 14 years. During his postdoctoral studies at the University of Pennsylvania, he also became heavily involved in the open-source 3-D printing movement, and his work at Rice combines both.

"Ultimately, we'd like to 3-D print with living cells, a process known as 3-D bioprinting, to create fully vascularized tissues for therapeutic applications," said Miller, assistant professor of bioengineering. "To get there, we have to better understand the mechanical and physiological aspects of new blood-vessel formation and the ways that bioprinting impacts those processes. We are using 3-D bioprinting to build tissues with large vessels that we can connect to pumps, and are integrating that strategy with these iPS-ECs to help us form the smallest capillaries to better nourish the new tissue."

Each of the trillions of living cells in the human body are constantly supplied with oxygen and nutrients by tiny blood vessels known as capillaries. Measuring just a few thousandths of a millimeter in diameter, some capillaries are so narrow that individual blood cells must squeeze through them in single-file. Capillaries are made entirely from networks of endothelial cells, the type of cell that lines the inner surface of every blood vessel in the human body.

In the process of tubulogenesisthe first step to making capillariesendothelial cells undergo a series of changes. First, they form small, empty chambers called vacuoles, and then they connect with neighboring cells, linking the vacuoles together to form endothelial-lined tubes that can eventually become capillaries.

"We expect our findings will benefit biological studies of vasculogenesis and will have applications in tissue engineering to prevascularize tissue constructs that are fabricated with advanced photo-patterning and three-dimensional printing," said Dickinson, the Kyle and Josephine Morrow Chair in Molecular Physiology and Biophysics at Baylor College of Medicine and adjunct professor of bioengineering at Rice.

In the study, Calderon, Rice undergraduate Patricia Thai and colleagues investigated whether commercially available endothelial cells grown from iPSCs had tubulogenic potential. The test examined this potential in two types of semisolid gelsfibrin and GelMA. Finally, the researchers also investigated whether a second type of stem cell, human mesenchymal stem cells, could improve the likelihood of tubulogenesis.

Calderon said fibrin was chosen for the experiment because it's a natural material that's known to induce tubulogenesis for wound healing. As such, the researchers expected endothelial cells would be induced to form tubules in fibrin.

Calderon said the first step in the experiments was to develop a third-generation lentivirus reporter to genetically modify the cells to produce two types of fluorescent protein, one located only in the nucleus and another throughout the cell. This permanent genetic modification allowed the team to noninvasively observe the cell morphology and also identify the action of each individual cell for later quantitative measurements. Next, the cells were mixed with fibrin and incubated for a week. Several times per day, Calderon and Thai used microscopes to photograph the growing samples. Thanks to the two fluorescent markers, time-lapse images revealed how the cells were progressing on their tubulogenic odyssey.

Calderon conducted advanced confocal microscopy at the Optical Imaging and Vital Microscopy Core facility at Baylor College of Medicine. Calderon and Thai then used an open-source software called FARSIGHT to quantitatively analyze the 3-D growth patterns and development character of the tubulogenenic networks in each sample. In fibrin, the team found robust tubule formation, as expected. They also found that endothelial cells had a more difficult time forming viable tubules in GelMA, a mix of denatured collagen that was chemically modified with methacrylates to allow rapid photopolymerization.

Over several months and dozens of experiments the team developed a workflow to produce robust tubulogenesis in GelMA, Calderon said. This involved adding mesenchymal stem cells, another type of adult human stem cell that had previously been shown to stabilize the formation of tubules.

Miller said that while clinical applications of 3-D bioprinting are expected to advance rapidly over the next few decades, even small tissue samples with working capillary networks could find use much more quickly for laboratory applications like drug testing.

"You could foresee using these three-dimensional, printed tissues to provide a more accurate representation of how our bodies will respond to a drug," Miller said. "Preclinical human testing of new drugs today is done with flat two-dimensional human tissue cultures. But it is well-known that cells often behave differently in three-dimensional tissues than they do in two-dimensional cultures. There's hope that testing drugs in more realistic three-dimensional cultures will lower overall drug development costs. And the potential to build tissue constructs made from a particular patient represents the ultimate test bed for personalized medicine. We could screen dozens of potential drug cocktails on this type of generated tissue sample to identify candidates that will work best for that patient."

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More information: G. A. Calderon et al. Tubulogenesis of co-cultured human iPS-derived endothelial cells and human mesenchymal stem cells in fibrin and gelatin methacrylate gels, Biomater. Sci. (2017). DOI: 10.1039/C7BM00223H

Jelena Rnjak-Kovacina, and her team at the University of New South Wales and Tufts University in the USA, are using silk to grow blood vessels.

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Angiogenesis is also how many cancers end up growing large enough to kill you.

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Call to bioscientists: choose and use your chemicaI probes very carefully – The Institute of Cancer Research (blog)

Our article is written for a bioscience audience and offers guidance on best practice in chemical probe selection, evaluation and use.

I have previously postedabout how small molecule chemical probes of high quality are crucial for investigating the function of proteins in cells and organisms and also for validating them (or not) as drug targets. This applies to all areas of biomedical research see articles by Stephen Fryeand Mark Bunnage and colleagues.

My colleague Julian Blagg and I have today published a Perspective on choosing and using chemical probes in the journal Cancer Cellthat is written specifically with the audience of biologists in mind.

There are numerous examples of how the use of fit-for-purpose chemical probeshas led to important discoveries in biomedical research. The value of chemical probes is particularly well demonstrated in the field of cancer research.

A good case in point is the relatively recent rapid growth in our understanding of the biology and pharmacology of bromodomains that was triggered by the discovery of potent chemical probes such as JQ1and I-BETand their closely matched inactive partner compounds used as controls.

Yet in my earlier blogI also drew attention to how loose standards in the selection and use of chemical probes are leading to serious errors in biomedical research studies.

To be effective as chemical probes, small molecule agents need to be cell permeable and to bind potently (i.e. strongly at low concentrations) to the desired protein target and modulate its function in the cell as measured by direct target interaction and appropriate downstream biomarker changes. And they also need to bind selectively, meaning that they dont interact with and modulate other cellular targets or more realistically that they only affect an acceptable number of additional relevant proteins.

However, use of poorly selective, or otherwise unsuitably flawed even frankly dreadful chemical compounds is widespread. This is sloppy science and contributes to what is often referred as a crisis in the reproducibility and robustness of biological findings.

Moreover, recent calculations have suggested that spending $150 on a poor quality, out-of-date chemical compound from a vendor catalogue, instead of buying a high quality chemical probe, can cost the scientific community billions of dollars. There are at least200 historic compoundsthat are often used and should be replaced with better probes.

So misuse of chemical probes is wasting scientists time and money and in many instances is undoubtedly leading to delays in the discovery of much needed medicines.

I explained in my previous posthow, in a Commentary article in the journal Nature Chemical Biology by Arrowsmith et alpublished in August 2015, an international panel of chemical biology scientists (of which I was a member) had issued a call-to-arms aimed at eliminating the use of substandard research tools in biomedical research and promoting best practice. That call was linked with the launch of a new community-based, 'TripAdvisor-style' online resource available at the Chemical Probes Portal.

The non-profit Portal works by offering online expert annotation and recommendations for use of chemical probes for particular molecular targets. These are provided by a Scientific Advisory Board (for full disclosure I am a member of this and a Board Director) with about 400 probes assessed to date.

Theres no doubt that great progress has been made in discovering high quality tools for cancer biology and target validation. Unfortunately two years on now from the publication of the Arrowsmith et al paper and the initial launch of the Chemical Probes Portal it is abundantly obvious that bad practice in the selection and use of chemical probes is still very widespread in biomedical research, including numerous, continuing high profile examples in cancer.

Its clear that biologists commonly choose chemical probes based on querying search engines such as Google which will lead them to vendor catalogues that provide variable levels of information, do not prioritize probes based on quality, and sometimesrecommend the same compound as a probe for different protein targets.

Alternatively, use of search engines like Google Scholar will return as top hits publications that are the most highly cited, but that also describe the oldest chemical probes. Such searches are less likely to find the best, usually more recent tools. For example, when Chemical Probes Portal staff looked at 10 compounds, randomly selected from the 200 no longer recommended historical probes listed on the Portal website, they found that since 2016 these past-their-sell-by date reagents have been used in 2,090 publications.

A specific illustration is the still very frequent use of one of the above historical compounds, LY294002 an initially valuable early inhibitor of the phosphoinositide 3-kinase lipid kinases (PI3 kinase) that was originally described in 1994. Although a usefulpathfinder probe,LY294002 exhibits only weak, micromolar potency for PI3 kinases and through chemoproteomic studies it was subsequently found to be active against numerous members of the PI3 kinase family, and also other unrelated proteins including bromodomains.

LY249002 has been cited in over 30,000 publications; moreover despite its poor potency and selectivity and its supersedence by severalsuperior compounds as chemical probes for PI3K, a recent search for LY294002 on Google Scholar returned 1,190 publications for the year 2016 alone and this now outdated and flawed probecontinues to be sold by many commercial vendors.

Its clear then that we need to find a way make things change and especially influence behaviour of biological research community which is the main user group for chemical probes. This is why Julian Blagg and I have written our Perspectivein way that we hope will get the message out to biologists.

As we say in the Abstract of the Perspective:

Small-molecule chemical probes or tools have become progressively more important in recent years as valuable reagents to investigate fundamental biological mechanisms and processes causing disease, including cancer. Chemical probes have also achieved greater prominence alongside complementary biological reagents for target validation in drug discovery. However, there is evidence of widespread continuing misuse and promulgation of poor-quality and insufficiently selective chemical probes, perpetuating a worrisome and misleading pollution of the scientific literature. We discuss current challenges with the selection and use of chemical probes, and suggest how biologists can and should be more discriminating in the probes they employ.

Despite the efforts so far within the chemical biology community, we point out that we have been guilty of: largely preaching to the choir [meaning chemical biology specialists] and failing to connect to a really critical audience: namely, the wider cancer biology community who rely upon small-molecule tool compounds, often in harness with biological reagents, to interrogate cancer cell biology and who frequently draw important and highly impactful biological interpretations, whether correct or misleading, from such studies.

A topical example that we highlight in our Perspectiveis the initially erroneous discovery and validation of the proposed target MTH1 in cancer. MTH1 has a role in breaking down damaged metabolites called nucleotides in cells and thus preventing them from being incorporated into DNA and was first published as a cancer target in very high profile publications in the journal Nature.

Small molecule agents that were originally used to validate MTH1 include compounds TH287 and TH588 as well as S-crizotinib. We discuss in our Perspectivethe elegant publicationfrom AstraZeneca scientists that identifies three different chemical series of potent and highly selective chemical probes that clearly inhibit MTH1 in cancer cells but despite this have no therapeutic effect on cancer cells.

Furthermore, the same article shows that neither small interfering RNA (siRNA) reagents that deplete MTH1 nor CRISPR-mediated removal of MTH1 had any beneficial effect of cancer cells, pointing to off-target activity with the original siRNA reagent as well the chemical compounds used.

Furthermore, the blogger Derek Lowehas just a couple of days ago updated this story by discussing a new publication from researchers at Bayerwho discovered BAY-707, yet another highly potent and selective inhibitor of MTH1, and found it to have no therapeutic effect on cancers cells. Hence at this stage the balance of opinion strongly indicates that MTH1 is not a valid target for cancer treatment.

One piece of evidence in the AstraZeneca study that was particularly critical in invalidating the initial chemical probes was the demonstration that both TH287 and S-crizotinib killed cancer cell lines lacking MTH1 and subsequent protein screening workshowed that the binding of TH287 and TH588 to tubulin is responsible for their cytotoxic effects.

We provide in the Perspectiveseveral other examples of how the close integration of orthogonal chemical and biological tools can be very powerful, as in the case of studies on SWI/SNF chromatin remodelling complex components, the transcription factor HIF2 and the Jumonji family of histone lysine demethylases. In addition, we describe cautionary tales of the problems arising with uncritical use of claimed chemical probes for proteins including poly ADP ribose polymerases (PARPs; for which a flawed PARP compound progressed to the clinic and failed); the molecular chaperone HSP70; KRAS-regulated autophagy; and pan-steroid receptor co-activators.

We discusshow a gold-standard test to validate the functional on-target response to a chemical probe is to demonstrate reversal of the cellular effects of a proposed small molecule probe compound by mutation in the protein target that abrogates compound binding.

Another useful technique is to engineer the target to interact with chemical probes not recognized by the natural (so-called) wild-type protein. An additional approach now becoming common is to determine the effects of the chemical probe in cells where the proposed protein target has been removed by CRISPR technology.

We point outthat although Small molecules are from Mars, biological tools are from Venus, they are nevertheless part of the same overall universe, providing orthogonal and complimentary approaches to understanding biology and target validation a very powerful, multidisciplinary and essential toolkit for modern biomedical research.

Also in our Perspectivewe highlight and explain an important aspect of target binding selectivity that is rarely articulated in discussion of chemical probes that it is absolutely to be expected that most small molecules will generally interact with multiple biological targets in cells and organisms. By contrast, biological reagents, for example siRNA oligonucleotides and antibodies, are intrinsically more likely than small molecules to bind selectively to the desired biological target as a result of the greater breadth, complexity and thus specificity of their combined intermolecular interactions.

Of course there are also major problems with the use of insufficiently selective biological reagents and greater rigour in their use is important too as elegantly discussed recently by Bill Kaelin but biologists need to be even more critical in their use of small molecule probes because their smaller size and lower complexity means that at least some degree promiscuity is likely to be the rule rather than the exception. This tendency can be mitigated by careful design and optimization of the probe but even then rigorous and broad experimental testing for selectivity is essential.

Indeed, we strongly advisethe maxim of caveat emptor let the buyer beware! when choosing and using chemical probes for biological exploration and target validation.

In discussing the challenge of selectivity, we illustrate how the off-target effects can range from an interaction with one or two proteins perhaps but necessarily related to the target of interest through binding to tens of other targets, all the way to the extreme end of unacceptability where compounds are frequent hitters or chemical impostersthat have totally unacceptable features like indiscriminate chemical reactivity, aqueous insolubility and self-aggregation that make them worthless for biological research.

Hard to believe, but there are even isolated examples of vendors supplying the incorrect chemical compound and routine checking for evidence of authenticity is advisable. Related to this, in our Perspectivewe call for further efforts in the community to eliminate the especially egregious behaviour of publishing biological results without disclosing compound structures which of course means that the suitability of a probe cannot be assessed, nor can the claims be independently checked. Reviewers of submitted papers and grant applications as well as journal editors should be especially vigilant about this.

We recognize that for many if not most biologists these considerations of the selectivity of chemical probes are not part of their training or expertise. They may not have ready access to advice from chemical biology or medicinal chemistry colleagues. And they may find articles in the specialist chemical biology literature off-putting and full of jargon as most scientific disciplines are.

So in our Perspective we provide what we hope will be useful tools for biologists using chemical probes. Firstly, we include as Box 1a Glossary so that that any specialist terminology that cannot really be avoided is not too much of a turn-off.

We provide in Box 2a comparison of the desired selectivity profiles of chemical probes with those of approved drugs making the point that in comparison to drugs, chemical probes generally need to be even more selective than drugs so that probes can be used with confidence to modulate the intended target of interest.

In Box 3we summarize the factors that determine the fitness and quality of chemical probes and in Figure 2we present an overview of Dos and Donts for their selection and use. In particular, we strongly recommend taking a routinely sceptical approach, including the use of orthogonal chemical and biological reagents; the use of at least two different chemical series (chemotypes) of probe along with inactive control compounds; demonstration of potency and selectivity; and obtaining evidence for selective target engagement and modulation in cells (e.g. using thePharmacological Audit Trail).

We advise (on page 13 of the Perspective) strongly against a common and dangerous practice, which is to expose cells with ever increasing concentrations of a chemical probe until a desired cell effect (phenotype), usually cell death, is seen and then attributing this phenotype to the specific effect of the probe on the protein target under investigation.

Higher probe concentrations increase the likelihood of off-target effects and the general range that should not be exceeded is 10-20 micromolar to minimize non-specific effects. Accompanying biomarker evidence of target modulation is also important.

Alongside the general guidance provided in our Cancer Cell Perspective, we strongly recommend the use of the Chemical Probes Portalfor expert advice and ratings for specific probes and targets.

We likenthe provision of advice on the selection and use of chemical probes to ensuring the biological researcher avoids being equipped with the equivalent of a defective global positioning/satellite navigation system, as illustrated in the cartoon below:

Download a larger version of Professor Julian Blagg's cartoon (PDF, 51KB)

Caption: The right way and wrong way with chemical probes

We finish the Perspectivewith the following strong new call-to-action:

We need to maximize the promise and minimize the peril of chemical probes and this requires the broad research community to use high-quality chemical probes that have been critiqued with equivalent rigor to biological reagents. It is time to put our house in order and biologists as well as chemists have an important responsibility to do so.

Im grateful to my colleague and joint senior co-author of our Cancer Cell PerspectiveProfessor Julian Blaggfor his excellent collaboration and insights. We developed the content of the Perspective very much in partnership. I also thank Julian for drafting the cartoon illustration.

In addition, I thank many colleagues and collaborators for helpful discussions and input, including the anonymous reviewers of the Perspective, and those in the field whose outstanding work we have built upon.

Excerpt from:
Call to bioscientists: choose and use your chemicaI probes very carefully - The Institute of Cancer Research (blog)

Cancer Research Institute Announces $1 Million Technology Impact Award Winner – Immuno-Oncology News

Dongeun Huh, PhD, from the University of Pennsylvanias Department of Bioengineering, is the recipient of theCancer Research Institutes (CRI) inauguralTechnology Impact Awardto advance the field ofimmuno-oncology.

Huh will receive a $1 million grant paid over three years to develop a microchip-based research model that mimics human cancer and immune cell interactions, a technological innovation that has the potential to accelerate the development of effective immunotherapies across different types of cancer.

There is an urgent need within the research community for new ways to model, observe, and interrogate complex interactions between the human immune system and tumorsa dynamic interplay that current two-dimensional cell cultures and animal models cannot characterize optimally, Jill ODonnell-Tormey, PhD, CRIs chief executive officer and director of scientific affairs, said in apress release.

Dr. Huhs microchip-based human cancer models represent a highly innovative intersection of cell biology and microengineering, which, when applied to cancer immunotherapy research, may spur advances in our understanding of how malignant human tumors interact with the immune system and surrounding tissues, providing researchers with new insights that will lead to improved cancer treatments, she added.

Huh has teamed up with two University of Pennsylvania immunologists to carry out the project: E. John Wherry, PhD, and G. Scott Worthen, MD. Together, they will oversee the investigation of cancer-immune cell interactions using Huhs technology.

Huh and his colleagues will use new bioengineering technology to apply microfabrication techniques originally developed for manufacturing computer chips to create a cancer-on-a-chip micro-device, which would enable cultures to be made of patient cancer cells.

The model will be engineered to form a network of living blood vessels that simulate the same vessels that immune cells use to circulate inside our bodies. Using this platform, Huh expects to study the interactions between cancer cells with key components of the immune system involved in cancer elimination, such as macrophages and T-cells.

Huh believes the research will lead to discoveries that could pave the way for new strategies to treat cancer with immunotherapies. In addition, the model could be developed into a screening platform to test and predict the effectiveness and safety of new drug candidates without having to test them on patients first.

Dr. Huhs proposal is truly exciting in terms of its potential to make an impact on how cancer immunotherapy research is conducted as well as how we predict patient response to immunotherapy, said Mark M. Davis, PhD, professor of immunology at Stanford Universitys School of Medicine and chair of the CRI Technology Impact Awards scientific committee.

This is sorely needed, and we also think this project could help us develop strategies that will extend the benefits of immunotherapy to more and more patients, he added.

The CRI Technology Impact Award is a new program designed to offer scientists and researchers a platform for multidisciplinary collaboration to transform the field of immuno-oncology. Organizers hope to fund technologies that improve our understanding of the antigenic profile, cellular interplay, and mechanistic pathways within the tumor microenvironment that are critical for an effective anti-tumor response. By supporting the development of highly innovative technologies, the program aims to enable researchers to develop the next generation of cancer immunotherapies.

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Cancer Research Institute Announces $1 Million Technology Impact Award Winner - Immuno-Oncology News

Genetics: The Study of Heredity – Live Science

A chart shows the dominant and recessive traits inherited in successive generations of guinea pigs.

Genetics is the study of how heritable traits are transmitted from parents to offspring. Humans have long observed that traits tend to be similar in families. It wasnt until the mid-nineteenth century that larger implications of genetic inheritance began to be studied scientifically.

Natural selection

This is one of the last photographs taken of Charles Darwin, who developed the theory of evolution whereby changes in species are driven, over time, by natural and sexual selection.

In 1858, Charles Darwin and Alfred Russell Wallace jointly announced their theory of natural selection. According to Darwins observations, in nearly all populations individuals tend to produce far more offspring than are needed to replace the parents. If every individual born were to live and reproduce still more offspring, the population would collapse. Overpopulation leads to competition for resources.

Darwin observed that it is very rare for any two individuals to be exactly alike. He reasoned that these natural variations among individuals lead to natural selection. Individuals born with variations that confer an advantage in obtaining resources or mates have greater chances of reproducing offspring who would inherit the favorable variations. Individuals with different variations might be less likely to reproduce.

Darwin was convinced that natural selection explained how natural variations could lead to new traits in a population, or even new species. While he had observed the variations existent in every population, he was unable to explain how those variations came about. Darwin was unaware of the work being done by a quiet monk named Gregor Mendel.

Inheritance of traits

In 1866, Gregor Mendel published the results of years of experimentation in breeding pea plants. He showed that both parents must pass discrete physical factors which transmit information about their traits to their offspring at conception. An individual inherits one such unit for a trait from each parent. Mendel's principle of dominance explained that most traits are not a blend of the fathers traits and those of the mother as was commonly thought. Instead, when an offspring inherits a factor for opposing forms of the same trait, the dominant form of that trait will be apparent in that individual. The factor for the recessive trait, while not apparent, is still part of the individuals genetic makeup and may be passed to offspring.

Mendels experiments demonstrated that when sex cells are formed, the factors for each trait that an individual inherits from its parents are separated into different sex cells. When the sex cells unite at conception the resulting offspring will have at least two factors (alleles) for each trait. One inherited factor from the mother and one from the father. Mendel used the laws of probability to demonstrate that when the sex cells are formed, it is a matter of chance as to which factor for a given trait is incorporated into a particular sperm or egg.

We now know that simple dominance does not explain all traits. In cases of co-dominance, both forms of the trait are equally expressed. Incomplete dominance results in a blending of traits. In cases of multiple alleles, there are more than just two possible ways a given gene can be expressed. We also now know that most expressed traits, such as the many variations in human skin color, are influenced by many genes all acting on the same apparent trait. In addition, each gene that acts on the trait may have multiple alleles. Environmental factors can also interact with genetic information to supply even more variation. Thus sexual reproduction is the biggest contributor to genetic variation among individuals of a species.

Twentieth-century scientists came to understand that combining the ideas of genetics and natural selection could lead to enormous strides in understanding the variety of organisms that inhabit our earth.

Mutation

Historically, scientists have defined living creatures by the presence of DNA, but how living creatures process information may be a better hallmark of life, a new study argues

Scientists realized that the molecular makeup of genes must include a way for genetic information to be copied efficiently. Each cell of a living organism requires instructions on how and when to build the proteins that are the basic building blocks of body structures and the workhorses responsible for every chemical reaction necessary for life. In 1958, when James Watson and Francis Crick described the structure of the DNA molecule, this chemical structure explained how cells use the information from the DNA stored in the cells nucleus to build proteins. Each time cells divide to form new cells, this vast chemical library must be copied so that the daughter cells have the information required to function. Inevitably, each time the DNA is copied, there are minute changes. Most such changes are caught and repaired immediately. However, if the alteration is not repaired the change may result in an altered protein. Altered proteins may not function normally. Genetic disorders are conditions that result when malfunctioning proteins adversely affect the organism. [Gallery: Images of DNA Structures]

In very rare cases the altered protein may function better than the original or result in a trait that confers a survival advantage. Such beneficial mutations are one source of genetic variation.

Gene flow

Another source of genetic variation is gene flow, the introduction of new alleles to a population. Commonly, this is due to simple migration. New individuals of the same species enter a population. Environmental conditions in their previous home may have favored different forms of traits, for example, lighter colored fur. Alleles for these traits would be different from the alleles present in the host population. When the newcomers interbreed with the host population, they introduce new forms of the genes responsible for traits. Favorable alleles may spread through the population. [Countdown: Genetics by the Numbers 10 Tantalizing Tales]

Genetic drift

Genetic drift is a change in allele frequency that is random rather than being driven by selection pressures. Remember from Mendel that alleles are sorted randomly into sex cells. It could just happen that both parents contribute the same allele for a given trait to all of their offspring. When the offspring reproduce they can only transmit the one form of the trait that they inherited from their parents. Genetic drift can cause large changes in a population in only a few generations especially if the population is very small. Genetic drift tends to reduce genetic variation in a population. In a population without genetic diversity there is a greater chance that environmental change may decimate the population or drive it to extinction.

Mary Bagley, LiveScience Contributor

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Genetics: The Study of Heredity - Live Science