Photo: Julio Sosa

While Penn offers nearly 90 majors at the undergraduate level, some are more attractive than others at least on paper.

According to education site College Factual, some of the most popular majors at Penn are finance, business administration and management, economics, nursing and biology.

Wharton sophomore Victoria Sacchetti, who intends to concentrate in finance, was attracted to the program due to her interest in quantitative data.

I love being able to analyze stocks and see how the market is impacted by different things such as politics, she said.

She added that she thought the applicability of her field and the skill of finance professors in the Wharton School served to draw other students to the major.

College sophomore Julia Hines first became interested in economics during high school. Since arriving at Penn she said that she has grown to appreciate the versatility of the major.

I think many people are attracted to econ because it is such a marketable and applicable major, and econ graduates have a wide range of career options, she said.

Anne Duchene, an economics lecturer, also emphasized the marketability of an economics degree.

[Economics] teaches how to analyze, understand and think critically. Employers know that, she said. And that's why they express so much interest in economics majors so students know that the job opportunities are everywhere, not only in bank and consulting, but also in non for profit, government, etc.

Nursing, which may seem more like a degree, is in fact a major in Penn's School of Nursing, and one of the most popular ones. Other majors offered by the School of Nursing include nutrition, which is hosted in partnership with the College of Arts and Sciences, and Nursing and Health Care Management, which is offered as part of a dual-degree program with Wharton.

For Nursing sophomore Jessica Korducki, one of the most appealing aspects of the Nursing School is the accelerated style of the program. While many nursing programs in other schools require students to take foundational classes before applying to major in nursing, Penn allows you to take nursing courses even during freshman year.

Welcome back to school! Read our other stories on NSO including a map on where to hit the books once NSO is over and an investigation into what actually happens when students skip mandatory NSO events.

Wharton sophomore Rachel Trenne's said she intends to pursue a management concentration in Wharton because she appreciates the big picture aspect of businesses.

Being able to learn about all the different elements of business and how they impact overall decisions and strategy is really interesting to me, she said, adding that she thinks the management concentration is particularly appealing to qualitative thinkers.

For students in the College, biology is the most popular choice.

College sophomore Olivia Crocker said the biology major is particularly important for those, like herself, who are interested in scientific research. She works part time at a laboratory during the academic year and worked there full-time over the summer.

Biology professor Linda Robinson identified several other factors that contribute to the popularity of the major. These include a widespread general interest and aptitude in science and math, fascination with the natural world [and] cool new discoveries," as well as "the perception that there may be a good job market for those trained in Biology, including the medical field," she said.

Crocker said the major is also particularly popular among pre-med students, though she's personally not interested in hat path.

Im interested in cell biology because it is more related to the small-scale molecular interactions that form the basis of life, rather than more large scale, anatomical basis of life that I feel is more emphasized in the medical field," she said.

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Out of 89 majors, Economics and Biology are two of the most popular. - The Daily Pennsylvanian

The larval Drosophila chordotonal organ seen under the scanning electron microscope. This sensory functional unit modulates the processing of mechanical stimuli by means of the latrophilin receptor. Scale: 10 m. Credit: Scholz et al., 2017

About two years ago, scientists from the University of Wrzburg discovered that a certain class of receptors is capable of perceiving mechanical stimuli. Now they have begun to unravel the molecular mechanisms behind the discovery.

The receptor studied by scientists from the universities of Wrzburg and Leipzig over the past years works similarly to the volume control of a stereo which enhances or attenuates the incoming signal. The receptor in question is called latrophilin/CIRL.

A little more than two years ago, the researchers had surprised the scientific community by proving that certain receptors, including latrophilin, respond to mechanical stimuli from the environment for example vibration, sound waves or expansion. By doing so, the receptors help organisms to hear, perceive movements and control their own movements.

How the information gets inside the cell

At the time, however, the details of the receptors' contribution were still unclear, i.e. how the process works at the molecular level. In the meantime, the researchers have been able to shed light on some crucial details. They present their results in the current issue of the scientific journal eLife. The lead authors of the study are Dr Robert Kittel, who heads a working group at the Institute of Physiology/Department of Neurophysiology at the University of Wrzburg, and Professor Tobias Langenhan, who recently relocated from Wrzburg to the University of Leipzig.

"In order for cells to perceive and respond to external stimuli, the information must somehow get inside the cell," Robert Kittel explains the central aspect of the study. This may be accomplished through ion channels where a mechanical stimulus is converted into an electrical response in a very straightforward and fast process.

With the latrophilin receptor things are different: "It does not form a channel and it does not forward the stimulus electrically," Kittel says. Instead, it activates intracellular messengers that trigger special signal cascades inside the cell which ultimately also affect the ion channels. According to Kittel, the receptor thus has a modulating effect on stimulus perception like some kind of volume controller.

Collaboration with numerous experts

The study just published is the result of collaborating with specialists from various domains at the University of Wrzburg an aspect which Robert Kittel particularly appreciates.

One of the contributing experts is the plant physiologist Professor Georg Nagel who was one of the scientists who discovered a celebrated technique which became known as "optogenetics". The underlying principle: Nagel characterizes ion channels and enzymes that can be controlled with light. Robert Kittel and Tobias Langenhan used the larvae of Drosophila, the fruit fly, for their experiments which are almost transparent so that the researchers were able to study the functioning of the receptors with simple flashes of light.

The second expert involved was Professor Markus Sauer, head of the Department of Biotechnology and Biophysics at University of Wrzburg's Biocenter. With his team, Sauer developed special forms of high-resolution fluorescence microscopy. This "super resolution" microscopy allows imaging cellular structures and molecules with up to tenfold increased resolution compared to conventional optical microscopes. "By using super-resolution microscopy, we were able to pinpoint the position of the cell membrane where the receptor is located," Robert Kittel says.

Dr. Isabella Maiellaro and Professor Esther Asan are also specialists in the field of imaging procedures. By teaming up with Isabella Maiellaro from the Department of Pharmacology, the researchers were able to directly visualize the intracellular receptor signal. Esther Asan, Professor at the Institute of Anatomy and Cell Biology II at the University of Wrzburg, also contributed to the success of the study with her expertise in electron microscopy.

Moreover, the project was supported by the extensive experience of Professor Matthias Pawlak at the Institute of Physiology of the University of Wrzburg in the field of sensory physiology and Dr Simone Prmel, a pharmacologist at the University of Leipzig. Robert Kittel sees these collaborations as a good example of how modern biotechnological methods can help answer physiological questions.

A very important molecular family

Latrophilin/CIRL is a member of a family of molecules that has more than 30 members in humans: the so-called adhesion GPCRs, a subgroup of the G protein-coupled receptors (GPCRs). Hundreds of them are encoded in the human genome; their importance is underpinned among others by the fact that around half of all prescription drugs target these receptors and help treat common diseases such as high blood pressure, asthma or Parkinson's.

This shows just how important the research results of the scientists from Wrzburg and Leipzig are. After all, knowing what is going on inside the cells is a prerequisite for developing a better understanding of pathological processes and designing new therapies. "The cell biology processes are well conserved in terms of evolution," Robert Kittel says. Similar mechanisms are also at work in human cells.

Robert Kittel and Tobias Langenhan are also members of a research unit funded by Deutsche Forschungsgemeinschaft (DFG FOR 2149) which studies the signalling behaviour of adhesion GPCRs. The current study harnesses the good experimental accessibility of Drosophila to bring new technologies into a biomedical context more quickly. This allows basic molecular mechanisms to be described for the first time. These mechanisms are now to be studied in further organisms and physiological contexts in collaboration with other scientists.

Explore further: Receptor dynamics provide new potential for pharmaceutical developments

More information: Nicole Scholz et al. Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons, eLife (2017). DOI: 10.7554/eLife.28360

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Molecular volume control - Phys.Org

UConn Health researchers developed and patented voltage-sensitive dyes that cause cells, tissues, or whole organs to light up as a result of electrical impulses and allow this activity to be measured. Now they have launched a startup to spread their product, which has potential in the process of drug discovery, beyond academia. Credit: Peter Morenus/UConn Photo

Vibrant tones of yellow, orange, and red move in waves across the screen. Although the display looks like psychedelic art, it's actually providing highly technical medical information the electrical activity of a beating heart stained with voltage-sensitive dyes to test for injury or disease.

These voltage-sensitive dyes were developed and patented by UConn Health researchers, who have now embarked on commercializing their product for industry as well as academic use.

Electrical signals or voltages are fundamental in the natural function of brain and heart tissue, and disrupted electrical signaling can be a cause or consequence of injury or disease. Directly measuring electrical activity of the membranes with electrodes isn't possible for drug screening or diagnostic imaging because of their tiny size. In order to make the electrical potential visible, researchers use fluorescent voltage sensors, also known as voltage-sensitive dyes or VSDs, that make cells, tissues, or whole organs light up and allows them to be measured with microscopes.

Not all dyes respond to voltage changes in the same way, and there is a common trade-off between their sensitivity and speed. Slower dyes can be used for drug screening with high sensitivity, but they can't measure the characteristics of rapid action potentials in some tissues, like cardiac cells. Fast dyes can be used to image action potentials, but they require expensive, customized instrumentation, and are not sensitive enough for crystal clear results on individual cells.

Professor of cell biology and director of UConn's Center for Cell Analysis & Modeling, Leslie Loew and his team have developed new fast dyes that are also highly sensitive, eliminating the speed/sensitivity trade-off.

Moving Ideas Beyond the Lab

Loew and research associates Corey Acker and Ping Yan have devoted much of their careers to developing and characterizing fluorescent probes of membrane potential like voltage-sensitive dyes. The team has even been providing their patented fast dyes to fellow researchers for the past 30 years, but they only recently became interested in commercializing their work.

To learn more about the science of entrepreneurship, they took advantage of several of UConn's homegrown programs. Loew and Acker's first step into entrepreneurship began in the fall of 2016, when they were accepted into UConn's National Science Foundation (NSF) I-Corps site, Accelerate UConn. They credit the program with giving them a solid foundation to evaluate their technology and business strategy.

Launched in 2015, Accelerate UConn aims to successfully advance more university technologies along the commercialization continuum. Under the auspices of the Office of the Vice President for Research and the Connecticut Center for Entrepreneurship and Innovation (CCEI), Accelerate UConn provides participants with small seed grants and comprehensive entrepreneurial training.

"Dr. Loew's experience is a prime example of how UConn can transform high-potential academic discoveries into viable products and services with the right training," says Radenka Maric, UConn's vice president for research. "Accelerate UConn helps our preeminent faculty move their ideas beyond the lab so they can join the ranks of other successful Connecticut entrepreneurs and industry leaders, and have an impact in our communities and on the state economy."

Acker says the program also helped them identify an exciting new market opportunity targeting pharmaceutical companies. These companies need dyes that are both fast and sensitive for high-throughput screening of potential therapeutic targets. In high-throughput drug screening, scientists create special cell lines, and then use advanced equipment to robotically apply different drugs to rotating dishes of cells. The cells are stained with a voltage-sensitive dye that displays any change in membrane potential or voltage after drug application with changes in fluorescence. Acker estimates that pharmaceutical companies and contract research organizations (CROs) spend over $10,000 on these dyes for each week-long study.

The dyes that Loew, Acker, and Yan develop will also allow drug companies to respond to new cardiac safety screening regulations from the Food and Drug Administration called CiPA (the Comprehensive in vitro Proarrythmia Assay).

CiPA regulations aim to establish better ways to detect side effects of new drugs that could cause a cardiac arrhythmia. In a key component of CiPA, screening is completed in cardiac cells with a realistic electrical heartbeat. The Loew team's fast-sensitive dyes could offer drug companies more effective options than are currently available. Since CiPA applies to any new therapies from weight-loss drugs to allergy medications, Loew and Acker anticipate high demand for their technology.

"We initially joined the Accelerate UConn program to learn how to build a business so we could sell our existing fast dyes to other scientists like us. Instead, we ended up discovering an entirely new customer segment with greater potential and more urgent need," says Acker. "We feel lucky to have had the opportunity to participate in this elite program based right here at UConn."

Gaining Outside Input

By following one of Accelerate UConn's most important tenets to "get out of the building," Acker conducted dozens of interviews with experts from industry who use VSDs for drug screening. They all expressed a need for dyes with improved sensitivity, faster speed, and fewer unwanted interactions or toxicity with the cells being tested.

Loew and his team were confident they could deliver.

Loew, Acker, and Yan's new dyes improve on the current sensors used for drug screening, which involve a two-component system and energy transfer between the components. The researchers produce dyes that use a novel VSD system where energy transfer is more efficient, resulting in faster, more sensitive, and less toxic dyes.

Loew says that support from UConn's entrepreneurship programs was pivotal in transforming their initial discovery from project to product.

"We learned so much from these programs, and we're still reaping the benefits," says Loew. "Targeting the right customer helped us gain additional research funding through UConn's SPARK Technology Commercialization Fund, and encouraged us to form a startup, Potentiometric Probes, to advance our product towards the market.

"We've been supplying VSDs to hundreds of cardiac and neuroscience research labs for over 30 years," he adds. "We're hopeful that Potentiometric Probes will assure that this continues, especially now that the demand is high and new commercial sector applications are emerging."

The team is currently developing a new website that will be a resource for researchers using these voltage imaging techniques. Once launched it will be accessible at http://www.potentiometrics.com.

Looking to the Future

Through their UConn SPARK Technology Commercialization funding, the team has been able to develop and test two new dyes, and they have conceptualized a few additional possibilities. One of their current prototypes is extremely promising, Loew says.

Loew and Acker are continuing to optimize their dyes and pursue follow-on funding to commercialize their products through the NSF's Small Business Innovation Research (SBIR) program and BiopipelineCT, which is administered by Connecticut Innovations.

They have also continued to grow as entrepreneurs by participating in the CCEI Summer Fellowship. Potentiometric Probes was named a finalist in this program, and will compete for an additional $15,000 prize in the Wolff New Venture Competition, also administered by CCEI.

The team members hope that one day their dyes will have a major impact for both the pharmaceutical industry and fellow university researchers.

"As academics," says Loew, "we don't really think about money. We're just happy to do our science and hope that it helps people one day. But considering the needs of an end user beyond other scientists will potentially lead to greater adoption of our discoveries, more funding for our projects, and ultimately more scientific breakthroughs. That's a culture change worth considering."

Explore further: New device improves measurement of water pollution

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Dyes detect disease through heartbeat signals - Phys.Org

Researchers have discovered a new way by which a gene mutation can kill neurons in people with ALS and a related disease, frontotemporal dementia, or FTD.

Their discovery, published in the journal Neuron, could offer researchers a new approach to treating these incurable conditions.

The gene mutation leads to the production of a faulty version of the TIA1 protein. The normal version facilitates what researchers call phase separation a process that allows cell components to assemble into membrane-less structures crucial to normal cell function.

When the protein malfunctions, the structures fail to disassemble, causing proteins to accumulate in nerve cells. This ultimately kills the neurons, researchers from St. Jude Childrens Research Hospital and Mayo Clinic said. They published their findings in an article titledTIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Their studyprovides a link to earlier observations that another protein, TDP-43, is often found in protein aggregates inALS patients.The researchers discovered that when TDP-43 was trapped in such protein assemblies, it became more insoluble.

This paper provides the first smoking gun, showing that the disease-causing mutation changes the phase transition behavior of proteins, Dr. J. Paul Taylor, chair of St. Judes Cell and Molecular Biology Department, said in a press release.

And the change in the phase transition behavior changes the biology of the cell, added Taylor, who led the study along with Dr. Rosa Rademakers of the Mayo Clinic operation in Jacksonville, Florida.

The path to discovering the importance of phase separation in amyotrophic lateral sclerosis started with a family that had ALS and FTD. The family had a mutated TIA1 protein. But when researchers discovered it some time back, they did not know what the implications of the mutation could be.

The studies, which included an analyses of the mutated proteins properties, led to the discovery that TIA1 mutations are common in people with ALS. When analyzing brains of deceased ALS patients who carried abnormal TIA1 genes, researchers found aggregates of what scientists call stress granules.

These TIA1-containing structures form when a cell is exposed to stressful conditions such as heat, chemical exposure, and aging.

The teams experiments revealed that TIA1 mutations made the protein stickier. This prevented the stress granules from breaking up and trapped TDP-43 in the process.

These findings are part of an emerging theme that there is a whole spectrum of diseases that includes ALS, and some forms of dementia and myopathy, that are caused by disturbance in the behavior of these structures that perturbs cellular organization, said Taylor, who said the results offer the first approach to treating ALS effectively.

Current therapies, which can slow the diseases progression only slightly, work by trying to improve the function of damaged neurons. In contrast, restoring phase separation may actually prevent nerve cell damage.

We know that these material properties are under tight regulation, so perhaps we dont have to target the disease-causing mutation itself, Taylor said. Perhaps we can restore balance by targeting any of a large number of regulatory molecules in the cell. There are already therapeutic approaches in laboratory testing that seek to do just that.

The team is now working on achieving a better understanding of phase transition properties. Their ultimate goal is to find ways to restore the processes, which may also be involved in other neurodegenerative conditions, including Alzheimers disease.

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ALS Mutation Kills Nerve Cells by Preventing Protein Clumps from Breaking Apart, Study Reports - ALS News Today

A gift from alumnus Paul Heidger 63, along with a matching grant from the Colorado Department of Higher Education, to provide $113,000 investment in UNCs honors program.

Heidger, a graduate of the universitys inaugural honors class, recently established the Barbara Heidger Opportunity Scholarship Endowment in honor of his late wife. The two met as honor students at UNC, then Colorado State College, when the institution created the honors program in 1959.

I sincerely hope this scholarship bearing Barbaras name, together with knowledge of her life story and accomplishments in education, in promotion of global awareness and peace, and in self-giving service to others may assist similarly inspired young women and men at UNC to reach their life goals and full potential, Paul said.

Heidger and his family established the fund to honor Barbaras legacy and her passion for international students. Earnings will be used to support current and incoming honors students, with a preference for those interested in international relations and education. Heidger plans to establish an additional honors program scholarship for students interested in science.

The generous giftfrom Paul and his family will provide supportfor years to come.These scholarships help UNC to recruit the best and brightest into our Honors Program, which seeks to develop tomorrow's problem solvers, said UNC Director for Honors and Scholars Loree Crow. Scholarship support of these motivatedstudents is essential to building the strongest cohorts and is invaluable to the individual students who often need just a little extra to help them succeed at their highest potential.

Paul Heidger 63 and Barbara (Hyslop) Heidger 63 first met as members of the inaugural Honors class, and the bonds and memories formed between them, their classmates and professors have lasted a lifetime.

At Paul and Barbaras wedding, fellow honors classmate, Bill Hayes, served as best man and classmate Sharon Wilson (now a UNC Professor Emerita) was one of Barbaras attendants. Dr. Eugene Koplitz, UNC professor and first honors program director, and honors Professor Dr. Forrest Frease and their families were honored guests.

Paul and Barbara were dedicated to their passions Pauls in biology and Barbaras in international affairs and both achieved accomplished paths of service to their professions. Barbaras untimely passing in 1994 at the height of her personal and professional life impacted family, students, colleagues and friends around the world. She was a devoted wife and mother to their daughters, Julie and Lisa, and a passionate educator and ambassador for international understanding. Paul recently retired from the University of Iowa, where he was a professor of Anatomy and Cell Biology.

Pauls initial gift of $60,000 created the endowment and, through a Colorado Opportunity Scholarship Initiative (COSI) grant from the Colorado Department of Higher Education, much of Pauls gift will be matched, bringing the total impact on the Honors Program to approximately $113,000. The Honors Program plans to use these funds to create scholarships for exceptional incoming freshmen and to attract more top honors students to UNC.

The Campaign for UNC goal is $45 million, and every dollar and every donor counts. Donors from across our community are contributing to the mission and success of UNC students, faculty and programs. Every gift matters. Gifts of all amounts are moving the mark and letting UNC's new generation know that Bears take care of Bears.

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First UNC Honors Alum Gives Back to Future Educators - UNCO News Central

Research team with (First left, back row) Prof Karl Herrup, Head of Division of Life Science; (Second right, back row) Prof Hsing I-Ming, Head of Department of Chemical & Biological Engineering; (First right, back row) Prof Michael Altman, Head of Department of Physics. Credit: The Hong Kong University of Science and Technology

Researchers at The Hong Kong University of Science and Technology (HKUST) have developed a new generation of microscope, which not only could capture 3D live cell videos, but the resulted images are also of much higher quality, greatly enhancing the accuracy and the scope of research on cell biology.

Researchers at The Hong Kong University of Science and Technology (HKUST) have developed a new generation of microscope, which not only could capture 3D live cell videos, but the resulted images are also of much higher quality, greatly enhancing the accuracy and the scope of research on cell biology.

While an existing confocal microscope can also capture 3D bio-images, the laser light hitting on the sample is typically one million times that of summer sunlight, such intense light exposure inevitably disrupts cell activities and eventually kills the cell, posing limits to the study of cell biology.

The LiTone Line Bessel Sheet (LBS) microscope invented by a team led by Prof Du Shengwang and Prof Michael Loy from HKUST, however, is 1,000 times less photo-toxic than the current confocal model, allowing the cell to live much longer for observation. Phototoxicity is a type of sensitivity induced by light, which could cause molecular changes. The new microscope is also about 1,000 times faster, allowing much higher temporal resolution for a smooth video taking. Scientists can then study how proteins are transported within cells with great accuracy and efficiency, and what happens when the cell becomes abnormal. Prof Du is a Professor from the Department of Physics and the Department of Chemical and Biological Engineering; he is also the Associate Director of the Super-Resolution Imaging Center. Prof Loy is an Emeritus Professor of Physics.

"It is a powerful technology out of sophisticated science and engineering, but we make it simple to users so that it can be operated by biologists with minimal amount of training," Prof Du said. "For the first time, scientists can study cells in much greater details. That could eventually help scientists unlock the mystery of how certain diseases were formed and developed in a cellular level."

Explore further: A microscope within a microscope

Provided by: The Hong Kong University of Science and Technology

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New technology to capture live cell images opening new possibilities to the study of cell biology - Phys.Org

Philip Howe Ph.D., the senior author on the Nature Cell Biology article, is chair of the Department of Biochemistry & Molecular Biology at the Medical University of South Carolina (MUSC) and the Hans and Helen Koebig Endowed Chair in Oncology at the MUSC Hollings Cancer Center Credit: Medical University of South Carolina

A mechanism that pushes a certain gene to produce a non-coding form of RNA instead of its protein-coding alternative can promote the growth of cancer, report researchers at the Medical University of South Carolina (MUSC) in an article published online ahead of print on August 21, 2017 by Nature Cell Biology. The non-coding RNA soaks up a microRNA that prevents epithelial-to-mesenchymal transition, one of the key features of tumor development.

From one gene, cells can often produce different forms of RNA. The exact pre-RNA copy of one strand of DNA in a gene must be cut and assembled into its final RNA form, or several forms, in a process known as alternative splicing. Yet while these alternative forms of RNA can encode different proteins, scientists are discovering that many types of RNA do not, instead performing vastly different functions that regulate cell fate and behavior. MicroRNAs, for example, home in on certain protein-coding RNAs and help degrade them.

It is another class, called long non-coding RNAs (lncRNA), that are of particular interest to Philip H. Howe, Ph.D., chair of the Department of Biochemistry & Molecular Biology, and the Hans and Helen Koebig Endowed Chair in Oncology at the MUSC Hollings Cancer Center. Howe and his team found that a pre-RNA for a protein called PNUTS can be alternatively spliced to form a lncRNA that contributes to cancer progression. The PNUTS lncRNA does not encode a protein, but rather soaks up like a sponge a certain microRNA that is usually tasked with preventing epithelial-to-mesenchymal transition, which is a key feature of tumor growth and metastasis.

Howe's group connected a number of dots to explain how this happens. First, they found that breast cancer cells contained more PNUTS lncRNA than normal breast epithelial cellsa good initial sign that the non-coding RNA was associated with cancer development. Those cells were also more mesenchymal, meaning that they were more likely to form tumors.

They next examined a ribonucleoprotein called hnRNP E1, which binds to pre-RNA and suppresses alternative splicing. Importantly, they knew that TGF-beta, which is released in large amounts by tumor cells, could prevent its binding, potentially allowing alternate forms to be made. Computer models predicted that this ribonucleoprotein could bind to PNUTS pre-RNA on its alternative splicing site. In lung and breast cancer cell lines, specially designed RNA probes confirmed that this exact splicing site was more exposed when the ribonucleoprotein was knocked down and that those cells had more PNUTS lncRNA. When cells were exposed to TGF-beta over time, PNUTS lncRNA was made in increasing amounts. It turns out that the ribonucleoprotein was bound more tightly with the alternative splice site. In normal conditions, this allowed PNUTS protein to be made, but in tumors, the alternative splice site became exposed and more lncRNA was made instead.

Yet the group wanted to confirm exactly how PNUTS lncRNA could encourage tumor formation. Additional computer simulations predicted that, based on its sequence, there were seven potential locations on the PNUTS lncRNA for microRNA-205 to bind. This microRNA binds and destroys a transcriptional regulator called ZEB1 that encourages cells to unstick from one another and spreada major step that allows epithelial-to-mesenchymal transition to occur. As predicted, without those potential binding locations, the lncRNA and the microRNA were unable to bind together. This helped cells stick together and spread less, even with TGF-beta added to push them to spread.

It appeared that PNUTS lncRNA was soaking up microRNA-205, which freed up ZEB1 to encourage cells to act more like tumors. To be sure that this was true, the group stuck fluorescent molecules to ZEB1 to track it and found that more of it was present when there were more PNUTS lncRNA.

As expected, preclinical models revealed that breast and lung tumors grew faster and larger when their cells contained more PNUTS lncRNA. By connecting all of the dots, Howe's group had shown that one gene can make either a protein-coding RNA or a long non-coding RNA. With TGF-beta, the lncRNA soaked up microRNA-205 like a sponge, freeing up ZEB to drive epithelial-to-mesenchymal transition, a critical event in the development and spread of cancer.

This is the first study to show exactly how TGF-beta drives cancer through formation of a long non-coding RNA. Howe and his team are conducting experiments to find other such long non-coding RNAs that follow this same mechanism in cancer, with the goal of developing therapies to target them.

"My prediction is that this mechanism didn't evolve to make just one long non-coding RNA," says Howe. "There are probably others that are generated in this same fashion."

Explore further: Long non-coding RNA modulates colorectal cancer metabolism

More information: A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression, Nature Cell Biology (2017). DOI: 10.1038/ncb3595

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How a non-coding RNA encourages cancer growth and metastasis - Medical Xpress

HYDERABAD, India, Aug. 21, 2017 /PRNewswire/ --At the 24th Congress & General Assembly of the International Union of Crystallography (IUCr), Bruker today announces the new, high-performance D8 VENTUREBIOTOOLS for laboratory macromolecular crystallography.

The D8VENTUREBIOTOOLS feature major advances in source, detector and sample handling technology:

Dr. Vernon Smith, the Business Development Manager for Macromolecular Crystallography at Bruker AXS, noted: "With the D8 VENTUREBIOTOOLS, Bruker has once again set new standards in crystallography systems for the home laboratory. Our extremely bright and stable ImSDIAMOND X-ray source and our large area PHOTONIII photon counting detector enable highly accurate data to be collected very quickly. By combining this unprecedented performance with fast, reliable handling automation, the new D8 VENTUREBIOTOOLS provide researchers the opportunity to move from crystal to structure more efficiently than ever before."

Professor Elena Conti, Director at the Max-Planck-Institute for Biochemistry in Martinsried, Germany, stated: "The D8VENTURE with METALJET has enabled my group to collect quality data from even our most difficult projects and has made our synchrotron trips more productive. With the addition of the new SCOUT sample changer, we expect this productivity to increase even further by being able to identify crystals suitable for structure determination more effectively. Taking less time to determine individual protein structures will enable us to push forward in our overall research goals more quickly."

About Bruker Corporation (NASDAQ: BRKR)For more than 55 years, Bruker has enabled scientists to make breakthrough discoveries and develop new applications that improve the quality of human life.Bruker's high-performance scientific instruments and high-value analytical and diagnostic solutions enable scientists to explore life and materials at molecular, cellular and microscopic levels. In close cooperation with our customers, Bruker is enabling innovation, productivity and customer success in life science molecular research, in applied and pharma applications, in microscopy, nanoanalysis and industrial applications, as well as in cell biology, preclinical imaging, clinical phenomics and proteomics research, clinical microbiology and molecular pathology research. For more information, please visit: http://www.bruker.com.

Investor Contact: Miroslava MinkovaBruker Head of Investor RelationsT: +1-978-663-3660, x1479E: rel="nofollow">miroslava.minkova@bruker.com

Media Contact: Dr. Heiko RessBruker AXS Director Marketing CommunicationsT: +49 (0)721-50997-0E: rel="nofollow">heiko.ress@bruker.com

The D8 VENTUREBIOTOOLS offer an unprecedented combination of high performance, low maintenance and low cost of ownership. The system incorporates the ISDIAMOND, the world's brightest microfocus X-ray source and the PHOTON III, a large area photon-counting X-ray detector. Its optional SCOUT robot can reliably handle 48 cryogenic samples automatically.

Keywords: macromolecular crystallography, X-ray detector, rotating anode

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Bruker Announces Novel D8 VENTURE BIOTOOLS for Advanced Structural Biology Research by X-Ray ... - Markets Insider

18 Aug 2017

When it rains, sometimes it pours. In the second paper describing taus ability to undergo liquid-liquid phase separation in the past month, researchers led by Markus Zweckstetter of the German Center for Neurodegenerative Diseases in Gttingen report that phosphorylation of tau dramatically enhances droplet formation, and that taus repeat domains play a key role in the process. In their August 17 paper in Nature Communications, the researchers made the case that droplets are an essential precursor in the formation of toxic tau tangles, though experiments were all conducted in cell-freeconditions.

Tau is one of many proteins involved in neurodegenerative disease that have been spotted mingling in liquid droplets (Oct 2015 webinar, Oct 2016 news). Inside the cell, the process of liquid-liquid phase separation (LLPS) leads to membrane-less organelles, including stress granules and the nucleolus. Interactions between proteinsespecially those donning low complexity domainsand nucleic acids trigger the process, and researchers have proposed the close quarters in the droplets could breed toxic aggregates, or derail essential cellular functions (May 2016 news). A recent study led by Kenneth Kosik and Songi Han of the University of California, Santa Barbara reported that tau coalesced into liquid droplets in a dish, and that interactions between positively charged tau and negatively charged RNA made the magic happen (Jul 2017 news). Researchers led by Anthony Hyman of Germanys Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, along with Bradley Hyman and Suzanne Wegmann of Massachusetts General Hospital in Charlestown, have also reported that tau forms droplets in vitro and in neurons (May 2017 news).

Fluorescently labeled tau (green) forms droplets at body temperature (bottom), but not at 5C (top). [Image courtesy of Ambadipudi et al., Nature Communications,2017]

In the current study, first author Susmitha Ambadipudi and colleagues investigated if, and under what conditions, tau undergoes LLPS, and how that relates to its propensity to aggregate into fibrils. They started by analyzing various regions of the tau protein with catGranule, a program that predicts propensity of a given protein region to undergo phase separation. While much of taus N-terminus scored low, its repeat domains scored high. The researchers therefore conducted most of their experiments using the K18 fragment of tau, which contains only the four repeatdomains.

They reported that under reducing conditions similar to those inside a cell, K18 formed a turbid solution. Bright field and confocal microscopy revealed K18 formed droplets under Goldilocks conditionsnot too cold (5C), not too hot (above 65C), but just right (37C). Under these conditions, K18 did not appear to form outright fibrils, although CD and NMR spectroscopy suggested the protein started exhibiting signs of b-sheet structure and that droplet-resident tau proteins formed tight molecular interactions, akin to amesh.

Could this mesh facilitate fibril formation under certain conditions? To get closer to answering this question, the researchers toggled multiple parameters, including temperature and pH, and added the polyanion heparin into the mix. They found that heparin triggered fibril formation most efficiently and under the very same conditions that facilitate LLPS, suggesting the two processes are linked. Polyanions have long been used to promote formation of tau fibrils (Goedert et al., 1996).

In the cell, tau occurs in six isoforms due to alterative splicing, and can be further processed by proteolytic fragmentation and a variety of post-translation modifications. How might these permutations affect LLPS? They found that droplet formation correlated with the number of repeats, and did not occur at all in an N-terminal fragment that lacked repeats. They also found that phosphorylation of repeat domains by the MARK2 kinase promoted LLPS. Notably, phosphorylated tau underwent LLPS at just 2 mM, a concentration similar to that inside of neurons. Interestingly, another recent study found that phosphorylation had the opposite effect on phase separation of the FUS protein, which plays a role in amyotrophic lateral sclerosis (Aug 2017 news).

In this proposed model of tangle formation, phosphorylation of tau promotes the formation of liquid droplets, which crowds tau, recruits polyanions, and triggers aggregation. [Courtesy of Ambadipudi et al., Nature Communications,2017]

The in vitro findings mesh with Kosik and Hans recent study, which found that tau formed droplets in the presence of RNA. Though Zweckstetter used heparin as a polyanion instead of RNA, both studies point to the importance of electrostatic interactions between tau and negatively charged molecules in promoting LLPS and aggregation. As a post-translational modification bearing a negative charge, phosphorylation may play a similar role, Zweckstetter pointed out. Zweckstetter added that phase separation of full-length, unphosphorylated tau did not occur in their hands. Mostly likely phosphorylation or interactions with RNA would be needed to facilitate that, he toldAlzforum.

The latter finding contradicts the findings of Wegmann and colleagues who did detect phase separation of full-length tau, and even of N-terminal tau completely devoid of repeat domains, she told Alzforum (May 2017 conference news). Wegmann was fascinated by this difference, adding that it underscores the complex process of phase separation, pointing to varying contributions of different regions of the tau protein in the process. For her part, Wegmann is working on pinning down the presence of liquid droplets of tau in cultured neurons, and in AD braintissue.

In a joint commentary to Alzforum, Kosik and Han agreed that understanding the physiological significance of these droplets was crucial: The in vitro studies lay the groundwork for the next big step: how might these phenomena operate in vivo where life is not only many-fold more complicated but rife with emergent properties.JessicaShugart

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More Droplets of Tau - Alzforum

56 million men and women in the US experience varying degrees of hair loss or baldness. Despite available medications and procedures, scientists are still striving to put an end to balding and the frustrations associated with it. Researchers from UCLAs Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research offered a new angle to solving hair loss problems: altering metabolic pathways of hair follicle stem cells. The study was published in Nature Cell Biology.

To understand how hair is lost, we must take a look on its growth cycle which has three components: the growth phase (anagen), a regression phase (catagen) and a resting phase (telogen). All hairs in our body undergo this cycle but the duration for each phase varies depending on the hairs location. For instance, the hair growing from our scalps will have 2-3 years of anagen, 2-3 weeks of catagen and about 3 months of telogen. Hairs from other body parts typically have shorter anagens but longer telogen phases.

Hair follicle stem cells (HFSC) are unspecialized skin cells that live inside hair-producing sacs called hair follicles. HFSCs are quiescent (meaning they are normally dormant) but they quickly activate during an anagen phase. Many factors regulate their quiescence but whenever they fail to activate as required, the rate of hair loss would exceed the rate of new hair growth. We lose an average of 100 scalp hairs daily and unnecessary disruptions in the hairs cycle lead to hair loss, hair thinning and other hair problems.

HFSCs have another important quality: they have a unique metabolic process. They metabolize glucose into a compound called pyruvate. Two things can happen to pyruvate: be sent to the mitochondria (the cells powerplant) to harvest energy or be converted to another compound called lactate.

The teams interest is to limit the entry of pyruvate into the mitochondria and see if this act will increase conversion to lactate, trigger activation of HFSCs and promote hair growth. To achieve that, they genetically altered two groups of mice differently. Subjects in the first group had their capacity for producing lactate erased; the mices HFSCs remained dormant. On the other hand, members of the second group were given the ability for higher-than-normal lactate production; the mice showed signs of activated stem cells and, eventually, they grew more hair! The study proved that there is a direct correlation between lactate production and hair growth.

The team then applied two drugs on mices skins to push the stem cells towards the lactate pathway. First was RCGD423 which increased lactate production and put the stem cells into an active state, thereby promoting hair growth. To do this, the drug utilizes a signaling pathway between the cells exterior and nucleus. Second drug was UK5099 which acts in a different way. It blocks pyruvates entry into the mitochondria thus forcing the stem cells to convert all their pyruvate into lactate, which also promotes hair growth. The provisional patents for these drugs are filed and covered by the UCLA Technical Development Group.

This isnt the first time a stem-cell-based treatment has been made for treating hair loss. While this discovery of stem cells relationship with hair growth (at least in mice) has big potential to be the cure for baldness weve been waiting for, the drugs are yet to be tested on humans.

Hair loss issues aside, one aspect that makes this research groundbreaking is the new information it added in the study of stem cells, particularly the link stem cells have with human metabolism. Aimee Flores, one of the author of the study, stated, The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

Read more:
Can Stem Cells Finally Solve Hair Loss? - Wall Street Pit