Researchers propose p-value change from 0.05 to 0.005 – University of Virginia The Cavalier Daily

In a forthcoming research paper from Nature Human Behavior, a group of scientists including University Psychology Prof. Brian Nosek propose to change the p-value threshold for statistical significance from 0.05 to 0.005 in order to enhance the reproducibility of data.

According to an article written by UCLA Biostatistics Prof. Frederick Dorey and published in the journal Clinical Orthopaedics and Related Research, a p-value is a calculated probability that tests a null hypothesis, a statement that expresses the opposite of the hypothesis being investigated in a scientific experiment.

This value is often required to be calculated in publishable research papers that compare quantitative data between two or more experimental groups, Chemistry Asst. Prof. Rebecca Pompano said.

A p-value allows scientists to determine statistical significance the notion that an experimental result is likely attributable to a specific cause rather than mere chance of their results. Smaller p-values suggesting strong evidence against the null hypothesis likely correlate with more precise data, indicating potential reproducibility and thereby credibility of a scientific experiment.

Presently, the accepted p-value for statistical significance rests at 0.05. As such, a p-values less than 0.05 represents statistical significance. This cutoff was arbitrarily determined by British statistician and geneticist Sir Ronald Fisher in the early 1900s.

Sir Ronald Fisher proposed it in one of his articles or books, Statistics Prof. and Chair of Statistics Karen Kafadar said in an email to The Cavalier Daily. As I recall, he tossed it off as If the probability of observing our data under our hypothesis is less than 0.05, we might consider that to be statistically significant. And that 0.05 seems to have stayed with us ever since.

A recent paper by a group of researchers from numerous academic institutions including the University of Southern California, Duke University, University of Amsterdam, University of Pennsylvania, Harvard University, Stanford University and the University of Virginia however, challenges the longstanding p-value of 0.05.

The lack of reproducibility of scientific studies has caused growing concern over the credibility of claims of new discoveries based on statistically significant findings, the paper, released as a preprint article on PsyArXiv last month, said. For fields where the threshold for defining significance for new discoveries is P < 0.05, we propose a change to P < 0.005. This simple step would immediately improve the reproducibility of scientific research in many fields.

This proposal seeks to encourage strength of evidence by calling probability values less than 0.005 significant and those between 0.05 and 0.005 suggestive, Nosek said in an email to The Cavalier Daily.

Current scientific literature varies in reliability between fields and research journals the primary sources of study publications. Commonly, lower-quality journals publish untrustworthy papers, as do some high-end elite journals, in which data presented may be cherry-picked by the investigator to present a case as more scientifically elegant than reality. These circumstances may be caused by a scientists lack of knowledge and proficiency in their field, or driven by an individuals desire for vocational success and economic incentive often furthered by larger numbers of publications, Biology Prof. Paul Adler said.

According to Pompano, the benefits of a stricter significance cutoff could include less false data in scientific literature. A lowered threshold could also reduce p-hacking, Asst. Biology Prof. Alan Bergland said.

In p-hacking, people can use websites or programs to find correlations between variables in their experiments, and this allows them to contort their results to fit their desired narrative, Bergland said. You can plot different variables against each other and come across correlations that are completely nonsense, but related. P-hacking would still be possible even if the threshold was lowered to 0.005, but certainly harder.

While the change in p-value may, by some extent, increase the reproducibility of data, researchers worry it could also inhibit scientific progress. A p-value of 0.005 is difficult to obtain when working with smaller sample sizes, which is often the case in pilot studies, human clinical trials and for ethical reasons when experimenting with live mammalian specimen, Pompano said. Ultimately, according to Adler, lowering the p-value would increase expenses, time needed to conduct experiments and false negatives results that incorrectly demonstrate absence of a particular condition within data.

Additionally, although a p-value can determine statistical significance, it is unable to predict the applicability of experimental data to human life.

It cannot tell you if the model for your data is right, or if your sample is representative of the population, or the probability that your hypothesis is true, Kafadar said. It can only tell you how consistent are your data with your hypothesis, assuming both that the sample is representative of the population and the model you are using is correct. If neither of those assumptions is true, the p-value may be misleading.

Due to such limits of the p-value, Adler and Pompano believe errors in experimental design the setup of a procedure undertaken to test a hypothesis are a more immediate source of defects in scientific validity. Both professors said a p-value change is unnecessary.

Essentially, you cant just look at a p-value and decide if the results are reproducible. You have to look at the question being asked and if the experimental design that was being performed actually allows you to answer that question at all, Pompano said. And then, does the data support the answer that the author has concluded? I think the p-value alone is one small piece of assessing the conclusion of the experiment.

In other fields examining non-binary hypotheses, such as experimental physics, a p-value is rarely utilized and therefore unrelated to reproducibility errors. Rather, systematic uncertainties like varying machinery usage and ill-defined experimental design play larger roles in empirical blunders.

According to Physics Prof. Blaine Norum, reproducibility errors often encountered in physics are due to differing equipment types and apparatus setup from lab to lab.

The question is not a statistical question, but a question of systematic uncertainties that is, machinery or experimental design which are not addressed by a p-value, Norum said. How equipment is set up, how one configures it to get measurements varies between people, leading to reproducibility errors from lab to lab. A p-value is a statistically derived quantity, and it doesnt address those issues.

Researchers have expressed that inconsistencies within published scientific data stem from flaws within the career structures of science, more specifically defined as an unstable job market and the immensely difficult nature of discovery, rather than statistical analyses.

In the structure of science, at least American science, a lot of the research is done by graduate students and post-doctoral fellows, so the only way for a faculty member to be successful and keep getting papers and grants is to have lots of people working for them theres a selective advantage to that, Adler said. But that only fuels the oversupply of scientists, meaning you have too many people chasing too few grant awards and people publishing less reliable data just for the sake of publishing a paper. And these problems are much more serious than the p-value.

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Researchers propose p-value change from 0.05 to 0.005 - University of Virginia The Cavalier Daily

New light cast on sea level, climate threats – Brunswick News

If it seemed like coastal flooding associated with king tides has been getting particularly worse in recent years, that is because it has, according to a new study by University of Florida scientists.

Essentially, a combination of weather factors and shifting atmospheric pressure pushed water up along the Atlantic coast south of Cape Hatteras, N.C., in what the authors call a sea-level rise hot spot.

King tides already cause regular incursions of seawater into many coastal communities, where continued (sea-level rise) is increasing the frequency of this so-called nuisance flooding, which may be further amplified by short-lived (sea-level rise) hot spots, the authors conclude in journal Geophysical Research Letters. We have demonstrated that (sea-level rise) hot spot anomalies are a recurring feature along the U.S. eastern seaboard related to the combined cumulative effects of (El Nio-Southern Oscillation) and (North Atlantic Oscillation) forcing.

The authors revealed they believe the cause of this sort of sea-level rise was similarly responsible for accelerated sea-level rise detected along the coast running from Massachusetts to North Carolina, something previously attributed to a slowing of a major Atlantic Ocean current.

This distinction is critical to the projection of (sea-level rise) along this heavily populated coastline and defines a new benchmark for ocean dynamic models to capture such a pattern of regional (sea-level rise) variability, the authors noted.

Meanwhile, a major federal climate change report receiving greater attention in recent weeks illustrates more clearly what researchers believe to be the factors driving long-term sea-level rise, along with other results from the effects of human behavior on the planet.

The last few years have also seen record-breaking, climate-related weather extremes, the three warmest years on record for the globe and continued decline in arctic sea ice, according to the Climate Science Special Report, a collaboration of 53 people across 13 agencies. These trends are expected to continue in the future over climate (multidecadal) timescales. Significant advances have also been made in our understanding of extreme weather events and how they relate to increasing global temperatures and associated climate changes.

Since 1980, the cost of extreme events for the United States has exceeded $1.1 trillion, therefore better understanding of the frequency and severity of these events in the context of a changing climate is warranted.

The report is part of the National Climate Assessment, something meant to take place every four years, but the NCA has only published three times in the 27 years since Congress passed the law creating it. And instructions on how to interpret the data into policy implementation will be a little more difficult, as Sunday the Trump administration disbanded the advisory committee tasked with that job.

Further, last week President Donald Trump signed an executive order reversing an Obama administration requirement that construction projects in coastal floodplains that receive federal dollars have to take into account sea-level rise and resulting flooding projections.

As predictions both get clearer and more dire from climate scientists, work is beginning to go into what might happen by the centurys end. Using a sea-level rise estimate of nearly six feet, Mathew Hauer leader of the University of Georgia Institute of Governments Applied Demography Program published a piece in the journal Nature Climate Change in April in which he estimates 13.1 million people in the United States could have to permanently move further inland.

Relationships between environmental stressors and migration are highly complex as press and pulse events trigger migration responses that range from short-distance temporary migration to permanent long-distance migration; some will move and others will not, Hauer wrote. (Sea-level rise) is unique among environmental stressors as the conversion of habitable land to uninhabitable water is expected to lead to widespread human migration without the deployment of costly protective infrastructure.

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New light cast on sea level, climate threats - Brunswick News

Clouds, rain can’t wash fascination with solar eclipse from eyes in Missouri – Topeka Capital Journal

AMAZONIA, Mo. Texans Lorin and Chris Matthews traveled from the Brazos River to a gravel road splitting corn and soybean fields adjacent to the Missouri River to lay eyes on the moon eclipsing the sun.

The roadside crew included their four children Allyriane and Sterling, 12; Zayn, 10; and Lachlan, 8 as well as Lorins sister, Liskin Kruse, and Kruses daughter, Meredith. The contingent tried out an array of flimsy disposable protective glasses Monday as the moon started nibbling away.

Its very bright, yellow and glowing, Zayn said in describing the cosmic spectacle.

What do you expect? said Sterling, with attitude blending solar analysis and sibling sarcasm. Its the sun.

Lorin Matthews, a physics professor at Baylor University in Waco, and Liskin Kruse, a biochemistry professor at the University of Kansas Medical Center, were drawn to Amazonia, purported population 318, for the sake of family and science. Kruse confessed to being a space wanna-be, while Matthews was bedazzled by the ability of researchers to predict the path of an eclipse with sufficient clarity to let everyone take part.

Its amazing we can predict with such accuracy the location of the sun, the earth and the moon, she said.

If only Mother Natures calibration of thick clouds and rainfall could be anticipated with surgical precision. About the same time the moon was to block out 99 percent of the sun, gray clouds descended on the hamlet of Amazonia and began spitting rain.

Among the dozen or so people parked in this speck of the eclipses hot zone, a few were lucky enough to catch a break in the clouds for split-second glimpses of the most poignant moments of totality, when only the corona of light around the sun can be visible. In this darkness, celebrants in the neighborhood shot off fireworks and firearms.

Allen and Valerie Cassavaugh, of Hopkins, Mo., were two of the visitors in Amazonia to witness the day dying and being reborn after a couple of minutes.

They plunked down lawn chairs next to their vehicle and worked on ham-and-cheese sandwiches and potato chips until the action started in a flat landscape with few trees on outskirts of St. Joseph, Mo.

The sky darkened as promised at totality, and the bizarre colors of sunset could be witnessed in several directions. Still, those clouds wouldnt cooperate.

It was worth the risk, Valerie said, since the next eclipse wont throw this much shade on the central United States until 2024.

Were 60 years old, Allen Cassavaugh said. Were not sure if well be around for the next one.

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Clouds, rain can't wash fascination with solar eclipse from eyes in Missouri - Topeka Capital Journal

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity. – UroToday

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, SMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Journal of cellular and molecular medicine. 2017 Aug 07 [Epub ahead of print]

Chiara Traini, Maria-Simonetta Fausssone-Pellegrini, Daniele Guasti, Giulio Del Popolo, Jacopo Frizzi, Sergio Serni, Maria-Giuliana Vannucchi

Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Department of Neuro-Urology, Careggi University Hospital, Florence, Italy., Department of Urology, Careggi University Hospital, Florence, Italy.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28782880

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Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity. - UroToday

Anatomy of a Goal: Giles Barnes Equalizer – Massive Report

Welcome to the Anatomy of a Goal, where each week we dissect one goal (or near goal) from the previous weeks Columbus Crew SC match.

For match 26 on the 2017 MLS Season, we take a look at Giles Barness 67th minute goal that put Orlando City SC level with Crew SC at 1-1, as part of the draw on Saturday.

Heres a look at the finish from the Orlando attacker.

After entering halftime up 1-0, the Black & Gold played on the back foot for much of the second half. New Designated Player signing Pedro Santos entered the match, but had little effect up to this point. The Lions goal seemed like it had been coming the entire half.

Orlando Citys equalizer began with center-back Tommy Redding picking up the ball just across the midfield line in his defensive half. Redding sees a wide open Cyle Larin (just to the right of the image) and plays an entry pass to the feet of the striker.

With the ball on the wing, Larin has space in front of him and can either play a pass to his strike partner Carlos Rivas, dribble the ball at Crew SC center-back Lalas Abubakar, or pass down the line to right back Scott Sutter.

The Columbus defense has a five-man backline, featuring both wing backs, with two defensive midfielders right in front of the center back trio.

Larin decides to carry the ball forward and is met by the Black & Golds newest addition, Santos. Under pressure, Larin once again has the same three options.

This time, Larin decides to slide the ball over to his right-back, Sutter, who is immediately defended by Waylon Francis. With the ball at his feet and no path forward, Sutter can pass the ball back into Larin, drop the ball back to Rivas, or dribble the ball backward to create more space.

Sutter finds Larin in the penalty box, who has his back to the goal and is defended by Abubakar.

With his back to the goal and Abubakar providing pressure, Larin has three options as Sutter cuts toward the goal. If Sutter is able to beat Francis, he can play a slotted pass to his right back, Larin can drop the ball back to Rivas or attempt to beat Abubakar off the dribble.

Sutters run goes nowhere, so Larin drops the ball back to Rivas.

Larins pass lacks pace, allowing Mohammed Abu to pressure the Orlando striker.

Rivas and Abu fight for the ball, and just as it looks like Abu might be about to set off on a Columbus counter attack . . .

. . . Rivas deflects the ball to teammate Cristian Higuita.

At the top of the triangle is the eventual goalscorer, Barnes. Wil Trapp is just to the left of Barnes, and should be marking the Lions attacker.

In the above video, Higuita uses an excellent turn to get around Abu, and send himself toward the goal and into a position to eventually slot the ball into Barnes.

Having left Abu behind, Higuita and Rivas both head toward the Black & Golds goal. Barnes is still near Trapp, though Trapp will totally abandon the midfielder.

With a touch from Rivas, Higuita continues his run forward. Abubakar leaves Larin to Francis and heads toward Higuita. Barnes begins his run in the channel between the Crew SC center backs. Trapp does not follow Barnes.

Here, Higuita can see that Barnes has beaten Trapp. If Higuita is able to beat Abubakar with a pass then Barnes should be in on goal.

In the middle of the 18-yard-box, Jonathan Mensah defends Dom Dwyer and holds Barnes onside.

Higuita plays a pass right between the legs of Abubakar as Barness has easily beaten Trapp. Trapp still hasnt attempted to recover from leaving Barnes open.

Here, is a quick video of Higuitas pass right between the legs of Abubakar. The Columbus center back leaves himself open for a nutmeg and Higuita makes the perfect pass right into the path of Barnes.

Just as Higuitas pass heads toward Barnes, you can see that the Orlando attacker was held onside by Jonathan.

From the side angle, Barnes was likely one to two yards onside as Higuita nutmegged Abubakar.

With only the goalkeeper between him and the goal, Barnes can continue dribbling forward, fire a quick shot or slot a pass into the path of Dwyer.

Barnes decides to keep dribbling and, once inside the six-yard-box, hits his shot from an incredibly difficult angle. Zack Steffen has cut off the near post, so Barnes must look to between the keepers legs.

The above video shots multiple angles of Barnes difficult shot. Steffen positions himself well, only leaving a difficult angle to the back post open for Barnes.

Barness shot just beats Steffen and Josh Williams . . .

. . . and caroms of the post for the equalizer from a difficult angle.

Findings:

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Anatomy of a Goal: Giles Barnes Equalizer - Massive Report

Molecular volume control – Phys.Org

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

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

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

Dyes detect disease through heartbeat signals – 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

Hendrix Genetics is an economic ‘win-win’ for GI – Grand Island Independent

The opening of Hendrix Genetics in Grand Island on Aug. 15 is an excellent example of the power of markets supplemented by appropriate government policy.

Feeding a growing world population now estimated to be 7.5 billion provides both a challenge and an opportunity as food producers endeavor to meet the growing demand for food. For Hendrix Genetics this demand represents opportunity as it is a world leader in turkey, layer and trout breeding as well as a major player in swine, salmon and guinea fowl production.

The numbers connected with Hendrix Genetics are impressive. They currently have 25 percent of the United States egg hatchery market and the new hatchery in Grand Island will serve 10 percent of the U.S. market. With good science and management, poultry production is an excellent way to provide quality food for both domestic and world markets.

Hendrix Genetics was willing and able to create the Grand Island plant because essential markets were available to meet their needs. After a nationwide search they determined that Grand Island was an excellent location. It provided needed isolation that was essential for the required biosecurity. In our area they found infrastructure for transportation needs, access to willing, affordable and capable labor and area producers to build and manage outlying barns as well as to provide feed.

For each component in the production process, prices, profits and wages had to be sufficient to bring together all the resources necessary to open and operate the plant.

Government policies had to align with needs of Hendrix Genetics and our community gave them an excellent invitation to grow our economy. The work of the Grand Island Area Economic Development Corporation was very important and we would add necessary and effective. Government and private enterprise had an effective partnership.

Also to be noted is that Hendrix Genetics is based in Holland and joins other industries in our community that are based in other countries such as New Holland-Italy and JBS-Brazil. Global interdependence is a reality and a plus for all those ready and willing to participate in the global economy.

America first may be effective political rhetoric in some parts of our country, but it is not good long term economic policy. Free trade and open borders will serve us better, particularly the food producers in the Midwest who are willing and able to feed the growing world population and rely on world markets.

This confluence of markets has added an $18 million investment to the city of Grand Island, more than 40 permanent jobs and an economic infusion estimated at $40 million.

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Hendrix Genetics is an economic 'win-win' for GI - Grand Island Independent

ETMC Cancer Institute to host women’s luncheon Sept. 12 – Jacksonville Daily Progress

The ETMC Cancer Institute will host Cancer, Genetics and You, a luncheon addressing what every woman should know about how genetics is changing cancer detection, on Tuesday, Sept. 12, at the CrossWalk Conference Center, located on the campus of Green Acres Baptist Church.

The event will feature keynote speaker Damini Desai Morah, MS, CGC, a genetic counselor and specialist from Myriad Genetics.

Science now identifies cancer as a genetic disease, meaning that cancer is caused by certain changes to genes that control the way our cells grow and divide, said Dianne Adelfio, vice president of the ETMC Cancer Institute. The speaker will discuss how your genetic makeup can affect your likelihood of developing cancers specific to women, as well as other cancers.

Attendees will be given a cancer genetic questionnaire to see if they should consider future testing. Cancer physicians and genetic specialists also will be on hand to answer questions.

Since 2015 the ETMC Breast Care Center has offered forms of genetic testing that involve taking a sample of blood or cheek mucosa to analyze a womans genes. The results can help women with breast cancer make treatment decisions, and alert them to risks of developing other cancers. Genetic testing for those who have not had cancer provides a better understanding of their own cancer risks including risks that can impact other family members.

Genetics is leading the way in medical advancements in cancer detection and targeted treatment, said Adelfio. This luncheon is designed to inform and inspire women to be healthcare advocates as they understand more about how the genetic code is providing a deeper understanding of cancer and helping save lives.

Tickets for the event are $20 per person or a table of eight for $150. Doors open at 11 a.m., with the program taking place from 11:30 a.m. to 1 p.m. Reservations are required and may be made online at etmc.org or by calling 903-535-6302.

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ETMC Cancer Institute to host women's luncheon Sept. 12 - Jacksonville Daily Progress