Culture

How is the retina formed? And how do neurons differentiate to become individual components of the visual system? By focusing on the early stages of this complex process, researchers at the University of Geneva (UNIGE), Switzerland, in collaboration with the École Polytechnique Fédérale de Lausanne (EPFL), have identified the genetic programmes governing the birth of different types of retinal cells and their capacity to wire to the correct part of the brain, where they transmit visual information. In addition, the discovery of several genes regulating nerve growth allows for the possibility of a boost to optic nerve regeneration in the event of neurodegenerative disease. These results can be discovered in the journal Development.

The visual system of mammals is composed of different types of neurons, each of which must find its place in the brain to enable it to transform stimuli received by the eye into images. There are photoreceptors, which detect light, optic nerve neurons, which send information to the brain, cortical neurons, which form images, or interneurons, which make connections between other cells. Though not yet differentiated in the early stages of embryonic development, these neurons are all produced by progenitor cells that, are capable of giving rise to different categories of specialized neurons. To better understand the exact course of this mechanism and identify the genes at work during retinal construction, researchers studied the dynamics of gene expression in individual cells. "To monitor gene activity in cells and understand the early specification of retinal neurons, we sequenced more than 6,000 cells during retinal development and conducted large-scale bioinformatic analyses," explains Quentin Lo Giudice, PhD student in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine and first author of this article.

Mapping a system under construction

In collaboration with Gioele La Manno and Marion Leleu of EPFL, the researchers studied progenitor's behaviour during the cell cycle as well as during their progressive differentiation. The scientists then mapped very accurately the different cell types of the developing retina and the genetic changes that occur during the early stages of this process. "Beyond their "age"--that is, when they were generated during their embryonic life--the diversity of neurons stems from their position in the retina, which predestines them for a specific target in the brain," explains Pierre Fabre, senior researcher in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine, who directed this work. "In addition, by predicting the sequential activation of neural genes, we were able to reconstruct several differentiation programs, similar to lineage trees, showing us how the progenitors progress to one cell type or another after their last division."

The researchers also conducted a second analysis. If the right eye mainly connects essentially to the left side of the brain, and vice versa, a small fraction of neurons in the right eye make connections in the right side of the brain. Indeed, all species with two eyes with overlapping visual fields, such as mammals, must be able to mix information from both eyes in the same part of the brain. This convergence makes it possible to see binocularly and perceive depths or distances. "Knowing this phenomenon, we have genetically and individually "tagged" the cells in order to follow each of them as they progress to their final place in the visual system," says Quentin Lo Giudice. By comparing the genetic diversity of these two neural populations, researchers discovered 24 genes that could play a key role in three-dimensional vision. "The identification of these gene expression patterns may represent a new molecular code orchestrating retinal wiring to the brain," adds Dr. Fabre.

Towards regenerative medicine

Even before the neurons reach the brain, they must leave the retina through the optic nerve. The last part of this study identified the molecules that guide neurons on the right path. Moreover, these same molecules also allow the initial growth of axons, the part of neurons that transmits electrical signals to the synapses and thus ensures the passage of information from one neuron to another, as well as about twenty genes that control this process. This discovery is a fundamental step forward for regenerative medicine.

The more we know about the molecules needed to appropriately guide axons, the more likely we are to develop a therapy to treat nerves trauma. "If the optic nerve is cut or damaged, for example by glaucoma, we could imagine reactivating those genes that are usually only active during the embryonic development phase. By stimulating axon growth, we could allow neurons to stay connected and survive," explains Dr. Fabre, who plans to launch a research project on this theme. Although the regeneration capacities of neurons are very low, they do exist and techniques to encourage their development must be found. Genetic stimulation of the damaged spinal cord after an accident is based on the same idea and is beginning to show its first successes.

In the field of computer engineering, magnetically switchable materials play a significant role in data storage. A team from the Cluster of Excellence Ruhr Explores Solvation at Ruhr-Universität Bochum (RUB) has developed and manufactured a novel molecule called 3-methoxy-9-fluorenylidene. What's special about it: its magnetic properties can be controlled through light of different colours. This might be of use for computer industry.

The researchers working with Professor Wolfram Sander at the Chair of Organic Chemistry II outline their findings in the journal "Angewandte Chemie" on 14 August 2019.

Broad application range of magnetic materials

Magnetism is indispensable in computer engineering. Magnetism controls, for example, the information flow from the computer to magnetic storage media such as hard disks. Moreover, magnetic storage devices use read/write heads in the form of magnets that identify (i.e. read), or alter (i.e. write) the magnetisation patterns on the hard disk.

Methoxy group controls magnetic properties

Developed by Wolfram Sander and his team, the organic molecule 3-methoxy-9-fluorenylidene is based on a fluorine scaffold with a methoxy group attached in the shape of a rotational tail.

The researchers have figured out that the molecule's magnetic properties are determined by the orientation of the methoxy group, which changes its conformation depending on the kind of light that hits it.

Blue light switches the methoxy group into the "up" conformation forming the diamagnetic and less reactive singlet state. Whereas green light rotates the methoxy group down at the molecule, which results in the paramagnetic triplet state that has a higher reactivity against molecular hydrogen.

Interesting for research and industry

Because of its properties, 3-methoxy-9-fluorenylidene is of great interest to research. "Using this group of atoms, we can study the spin dependence of reactions. It could also play a role in the development of novel switchable magnetic materials and chemical sensors," predicts Sander.

Compared with traditional ferromagnetic materials, 3-methoxy-9-fluorenylidene offers considerable advantages: magnetism can be switched on and off through visible light. Moreover, organic magnets are not brittle like conventional magnets, but flexible and can be processed like plastics.

The snag

However, the molecule does have one drawback: it is stable only at extremely low temperatures. "This is why we are researching into magnetically switchable materials that can be used under ambient conditions," says Wolfram Sander.

Several fungal species from the order Trichosporonales are of interest for industrial applications because they might be used for the production of biofuels. However, to explore their biotechnological potential it is necessary to learn more about their biology. An team of researchers led by Associate Professor Minou Nowrousian from the Department of Molecular and Cellular Botany of the Ruhr-University Bochum (RUB) has now analyzed 24 genomes of Trichosporonales fungi with a focus on genes that are important for sexual development. The study was performed in collaboration with the laboratory of Prof. Dr. Joseph Heitman from Duke University, USA, who has an ongoing collaboration with the RUB and has been a visiting professor with the RUB Research School

The researchers published their results in the journal "Plos Genetics" on 6 September 2019.

The genes that regulate sexual development in fungi are called mating type genes. They must differ between mating partners to allow successful cell fusion. In fungi of the basidiomycetes, which comprise the Trichosporonales, but also well-known mushrooms like the button mushroom, the mating type genes are often located at two different positions within the genome, which are called mating type loci. However, there are species with fused mating type loci, where both loci are physically linked on the same chromosome. The chromosomes that contain the mating type loci often have functions similar to sex chromosomes in animals and plants.

Discovery of novel features

The team from Germany and the USA has analyzed the mating type genes in 24 species of the order Trichosporonales, and discovered physically linked mating type loci with previously unknown features.

The results showed that all analyzed Trichosporonales species have fused mating type loci with properties that are different than the properties of previously analyzed fused mating type loci in other basidiomycetes. Both the order of the genes within the fused loci as well as the sequences of the genes are highly conserved, in contrast to fused mating type loci in other basidiomycetes. This is unusual, because mating type as well as sex chromosomes tend to degenerate during evolution. The mechanisms that stabilize the Trichosporonales mating type loci will be analyzed in future studies.

Is there a lottery ticket that always wins? So goes the popular version of a theoretical conundrum posed in 1969 by English mathematician Adrian R.D. Mathias within the field of set theory, an area dealing with infinity in mathematics.

The problem remained a mystery throughout the 70's, 80's and 90's, as set theorists the world over tried their best to solve it. Associate Professor Asger Dag Törnquist of the University of Copenhagen's Department of Mathematics was introduced to the problem in 2002 while completing his doctoral dissertation at the University of California, Los Angeles (UCLA).

"Research in the area had gone dormant from the 1990's on because no one was making any progress towards a solution. I was fascinated because it was an old problem that dealt with our understanding of infinity in mathematics. Even then, it became a dream of mine to solve the mystery, even though I had no idea of how to accomplish what had been elusive for others over decades," he says.

MAD families

Mathias researched order and structure, things that occur spontaneously in sufficiently large mathematical systems. Today, this is known as Ramsey Theory, named after British mathematician and philosopher Frank Ramsey. Mathias' research pointed out that there was a profound correlation between Ramsey Theory and what he called MAD families, but he was unable to prove the existence of such a relationship.

"A MAD family is can be thought of as a kind of lottery ticket that always wins in a peculiar, infinite lottery game. In this game, lottery tickets have an infinite number of rows of whole numbers, and each row itself has infinitely many numbers. And, a ticket may have so many rows that they simply cannot be numbered," says Törnquist.

What Mathias asked the math world was, if the order and structure that we know is there, as per Ramsey Theory results, prevent the existence of a MAD family, i.e., a ticket that always wins.

The 'baby-mystery' proved decisive

Asger Dag Törnquist's shouldered his dream of solving Mathias' question for several years abroad until he began working at the University of Copenhagen's Department of Mathematical Sciences in 2011. This marked the beginning of a period during which Törnquist and David Schrittesser, his Austrian postdoctoral researcher, would gradually approach the solution.

"In 2014, I decided to rethink the problem from scratch and found a whole new way of tackling it. Alongside the original mystery, Mathias had formulated a sort of baby-version of the mystery. Neither had been solved. I managed to solve the baby version of mystery, which I then wrote an article about," explains Törnquist.

As a result, a great many mathematicians from around the world reacted. The article suddenly reignited research in the area. Researchers in other parts of the world began to build upon the UCPH researchers' article and more and more pieces of the puzzle began falling into place.

"We were in the midst of writing an article meant to address yet another small piece of the puzzle, when we realized that we may have been closer to solving the entire riddle than we had believed. From then on, things moved quickly. A few weeks later, we had the solution," recounts the mathematician.

Solution: An ever-winning lottery ticket does not exist

After five years of work, Asger Dag Törnquist and David Schrittesser had their research article on Adrian Mathias' "lottery ticket" accepted to the prestigious American scientific journal, The Proceedings of the National Academy of Sciences (PNAS). The two researchers discovered that complete coincidence does not exist.

"We found out that lottery ticket numbers clump up in such a way that there is no certainty of a winner, which was what Mathias had guessed would happen, but had been unable to prove. This confirms that one cannot assemble such a type of a lottery ticket without the emergence of certain patterns and regularities in ticket numbers. As such, there is no lottery ticket that always wins Mathias' lottery game," concludes Asger Dag Törnquist.

Some of these changes are long-lasting and can be detected even days after neuronal activation, as a form of genomic memory of the past neuronal activation.

The research, conducted in rodents and published in Nature Neuroscience, shows new molecular mechanisms that contribute to the plasticity of the adult brain. The changes initiated by neuronal activation are more complex and act at more levels than previously thought.

These findings, carried out by an international team led by researchers from the Instituto de Neurosciencias, UMH-CSIC in Alicante, with the participation of researchers from Emory University in Atlanta, describe for the first time the changes in the organization of genetic material in hippocampal excitatory neurons from adult mice upon activation.

"We wanted to know how the activation of a neuron can changes its future response; those changes constitute a form of cellular memory essential for the formation of memories," explains Dr. Ángel Barco, a researcher at the UMH-CSIC Neurosciences Institute that has led the research. "To achieve this goal we have used several techniques in neurogenomic that are applied for the first time in an intact mouse brain," says Dr. Barco.

The researchers wanted to know specifically what happens in a neuron that activates when the animal is exposed to a new context. "This response is important for memory formation, but it is very difficult to address experimentally. The group of neurons that respond to an experience like this is very small group of diffusely distributed through the brain, therefore it is very difficult to isolate them and see what happens inside", adds Dr. Barco.

To simplify, researchers have taken a shortcut. They have caused massive activation of mouse neurons, as in an epileptic process, and have looked at the changes taking place in chromatin.

Chromatin is a highly compacted structure in which almost two meters of genetic material (DNA) is stored in the tiny nuclei of cells thanks to the action of special proteins called histones. To get an idea of the degree of chromatin compaction, about one hundred thousand cell nuclei fit on the head of a pin.

"The advantage of the epilepsy model is that we have a lot of starting material to perform the analysis. It is easy to have 10 million cells. If we want to go to the most complicated memory model, only scalable techniques that require little starting material will work, because in this case the network of neurons is formed by about 2,000 cells" says prof. Barco.

"With what we learned in the simulation of epilepsy, we have been able to confirm these changes in a more physiological situation, such as the activation of groups of neurons that take place in the brain of a mouse when exploring a new place," he adds.

The researchers saw that in both cases a transcriptional "burst" occurs. That is, a very strong activation of specific genes to produce proteins. Transcription is the first step of gene expression. It leads to the formation of proteins, which are the molecules that direct almost all vital processes.

In turn, the transcription of the genetic material depends on the changes that take place in the chromatin. The degree of compaction of that chromatin and the interactions between separate regions of the chromatin contribute decisively to regulate transcription and therefore gene expression.

This study, published in Nature Neuroscience, demonstrates that this activation is associated with an increase in accessibility and the appearance of new interactions between separate regions of chromatin, necessary to allow the activation of genes. "The dynamic and large-scale adjustments of the genome topology observed in our study probably contribute to the rapid and coordinated transcriptional response associated with neuronal activation in both normal and pathological conditions," explains Jordi Fernández-Albert, the first author of the study.

These changes - called epigenetic because they do not affect the information contained in the genetic material but their expression - can permanently modify the expression and future response capacity of the genes involved in cognition, thus representing a type of genomic memory.

These epigenetic fingerprints in the chromatin could represent an appropriate substrate for lasting changes in behavior. They could participate in the establishment of memories by influencing the future response of neurons to the same stimuli that caused the change or to different ones. In addition, some of these lasting changes could be related to brain disorders such as epilepsy and cognitive dysfunction.

New research from North Carolina State University finds that being convicted of a crime is associated with a decline in one's physical health, even if the conviction doesn't lead to jail time. The study also confirms previous work finding that being arrested is associated with adverse mental health outcomes, even if an individual isn't ultimately charged with a crime.

"Many people often think of low-level interactions with the justice system as being inconsequential," says April Fernandes, author of a paper on the work and an assistant professor of sociology at NC State. "For example, if someone is arrested and released, it's seen as 'no harm, no foul.'

"We're learning that there can be significant mental health effects from low-level contacts. And there can be significant physical health effects even when convictions are associated with probation or fines, rather than jail time."

For this study, Fernandes looked at data from a nationally representative sample of about 9,000 young people who participated in the National Longitudinal Survey of Youth 1997, focusing specifically on data submitted between 1999 and 2010. The study participants were between the ages of 18 and 32.

Specifically, Fernandes evaluated self-reported physical and mental health assessments to determine whether there was a change in reported health status associated with justice system contact. Fernandes looked at four types of contact for study participants: being arrested; being charged; being convicted; and being sentenced to jail time.

"People reported increases in depression and stress across the continuum of contact, from arrest to jail time," Fernandes says. "That's consistent with previous work.

"And we knew that jail time affects physical health, for a host of reasons. But the fact that convictions were associated with physical health effects is particularly interesting. It would be worth exploring what drives those outcomes in greater detail."

Scientists have found that brain networks develop differently in males and females at puberty, with boys showing an increase in connectivity in certain brain areas, and girls showing a decrease in connectivity as puberty progresses. These analyses were focused on brain regions previously identified as conferring risk for mood problems in adolescents, suggesting an association, although this needs to be tested. This work is presented at the ECNP Congress in Copenhagen, and is based on a recent peer-reviewed publication.

According to lead researcher, Dr Monique Ernst (National Institute of Mental Health / NIH, Bethesda, Maryland, USA), "In our study, we showed that certain brain regions develop differently in boys and girls at puberty. Functional connectivity increases in boys and decreases in girls over puberty. Our next set of studies will aim to clarify the significance of these communication changes in the maturing brain, and to identify if the changes are protective or if they increase vulnerability."

"We looked at these brain areas because they had previously been identified as conferring risk for mood problems in adolescents. We know that mood upsets, particularly anxiety and depression, occur disproportionately in girls, and that women are twice likely as men to suffer from depression following the trend emerging during puberty. We found that the puberty period is associated with significant brain changes in these mood-related brain areas; however, we need to be cautious in interpreting these changes; we need to verify that the association we see between these brain changes and the coincident mood changes are linked. This work is underway."

The researchers analysed brain scans of 147 girls and 157 boys, aged between 13 and 15, from centres in Dublin, London, Dresden, Mannheim, and Paris.They were at varying puberty stages, from having not started their puberty to being fully mature. The researchers took images of the brain activity while the adolescent volunteers were lying still in an MRI scanner. These images were corrected for age and then were analyzed in a way that measures how strongly brain regions communicate with one another (known as "functional connectivity"). The values of the functional connectivity of these regions were correlated with the level of maturity at puberty.

Monique Ernst continued, "This is a first, because in the past, brain scans of adolescents have mostly been measured against a relatively wide chronological age, whereas, here, we were able to measure brain changes directly against their puberty status. We found that for an equivalent change in puberty status, the functional connectivity in these specific brain areas increased in boys by an average of around 6.5%, but decreased in girls by an average of around 7.2% (both these results were statistically significant). Specifically, these brain areas are within the medial prefrontal cortex and the parietal cortex.

Collectively these findings indicate that there are opposite changes of brain activity in boys and in girls as they go through puberty, and this male/female developmental pattern can be a key factor in in the role of pubertal development in the emergence of mood disorders. The next critical next step is to examine the role of these brain connectivities in the development of depression as these adolescents get older, using a longitudinal design."

Commenting, Dr Jaanus Harro (Division of Neuropsychopharmacology, Department of Psychology, University of Tartu and Psychiatry Clinic, North Estonia Medical Centre, Tallinn), said:

"This is particularly interesting in terms of demonstrating connectivity differences between boys and girls. While depression is more prevalent in females it still does occur in males too frequently, while the formal diagnostic criteria are identical. However, the neural pathways to depression in males and females might be partly different, as increasing number of gene-environment interaction studies has shown different interactions in boys and girls, on occasion quite opposite to one other. This imaging study offers a potential brain correlate to these distinct interactions, and it is quite plausible that they might arise during adolescence."

Dr Harro was not involved in this work; this is an independent comment.

This is National Suicide Prevention Week, and John Campo--the chief behavior wellness officer at West Virginia University--is examining trends in suicide rates to make suicide prevention more effective. His recent findings suggest that rural residents may be especially vulnerable to suicide when they face economic challenges.

In a new study, published in JAMA Network Open, Campo and his colleagues analyzed county-level suicide trends in the United States from 1999 through 2016 for individuals between the ages of 25 and 64.

The research team discovered that socioeconomic deprivation disproportionately raised suicide rates in rural counties. In metropolitan counties, suicide rates did not increase as greatly when similar levels of deprivation were present. And although suicide rates are increasing overall, they're increasing the most--and the fastest--in rural counties. Their findings appear in JAMA Network Open.

"These findings align with recently observed declines in life expectancy for white, middle-aged Americans with lower levels of education that have been attributed to increases in deaths of despair due to suicide and substance use," said Campo, who serves as assistant dean for behavioral health--and professor of behavioral medicine and psychiatry--in the School of Medicine and Rockefeller Neuroscience Institute.

The researchers also found that higher social capital--such as an abundance of art and nature facilities, religious organizations and barber shops--correlated with lower suicide rates. In contrast, greater social fragmentation was associated with higher suicide rates. Examples of social fragmentation include high percentages of single-person households, unmarried residents and people who have lived in the community for less than a year.

The study assessed the impact of more than 50 contextual factors on county-level suicide rates. These ranged from measures of socioeconomic factors, such as each county's median family income, to measures of social capital, including the presence of charitable organizations, parks and recreational facilities.

Campo suspects one reason rural residents may be more vulnerable to such "deaths of despair" is that they see economic advancements bypassing their communities. "Advancements in information technology and alternative energy may be groovy but probably do little to help rural communities where farming and extractive industries like coal mining have been the rule," he said.

Why might people who live in rural counties be particularly susceptible to the effects of socioeconomic deprivation? Campo has a guess. "Folks in rural areas are more socially isolated. They face big challenges related to transportation and interpersonal communication. Some areas in West Virginia don't even have the internet. And they have difficulties accessing health and mental health services," he said. "In urban areas, you can be depressed, but you can walk to the corner store or get on the bus and go to the doctor. If you live in a holler somewhere and you don't have a car, you're out of luck."

Based on the study's findings, Campo speculates that improving rural residents' access to mental healthcare might improve outcomes. So might connecting them with 24/7 crisis assessment and management services. Enhancing how hospitals can assess and treat patients who arrive at the emergency department during a mental health crisis may also be beneficial. Advancements in communication and telemedicine might, too.

"How do we do a better job educating folks in rural settings about helplines they can call--about the things they can do that maybe people in urban settings know a little bit more about?" Campo said.

He thinks alleviating loneliness among rural residents would help as well. "How do you get people in rural communities to maybe volunteer or better engage with each other?" he said. "That's what I'd be thinking about. I think it's an opportunity for faith-based organizations. Anything that's going to bring people together and decrease isolation in a healthy way is probably going to be protective."

Data from individuals with different types of severe visual impairment suggest that the associations we make between sounds and shapes -- a "smooth" b or a "spiky" k -- may form during a sensitive period of visual development in early childhood. The findings are published in Psychological Science, a journal of the Association for Psychological Science.

"In congenitally blind participants, as well as in participants with a history of congenital or childhood developmental cataracts, we found no evidence of reliable sound-shape associations," says lead author Suddha Sourav of the University of Hamburg. "However, in late permanently blind individuals whose blindness began after 12 years of typical vision, we observed a typical sound-shape association for touched objects that was not significantly different from the typically sighted control group."

"The results provide evidence that commonly found associations between shapes and sounds depend on an extended developmental period during which high visual capabilities are required," Sourav explains. "However, once acquired, sound-shape associations seem to be robust and are not extinguished by blindness."

Philosophers and researchers alike have long been fascinated by the cross-modal associations humans almost universally make, linking features across sensory modalities. One of the most common cross-modal associations is sound-shape association as shown in the bouba-kiki effect, whereby people reliably associate pseudowords such as bouba with round shapes and pseudowords such as kiki with angular shapes.

Researchers have found evidence for the effect across cultural and ethnic groups, including the Namibian Himba tribe that does not use a written language, which raises the question of whether these associations are somehow innate or depend on sensory experience. Some studies have shown that sound-shape associations such as the bouba-kiki effect emerge very early in childhood, while other research indicates that individuals who are congenitally blind do not form these associations. Together with the new findings, the available evidence suggests that these cross-modal associations may only emerge within a sensitive developmental period in childhood.

To find out whether such a sensitive period exists, Sourav and colleagues recruited participants with different visual abilities and histories from the LV Prasad Eye Institute in Hyderabad, India, and the local community in Hamburg, Germany. The sample included 15 participants who were congenitally and permanently blind, 12 participants who became blind after the age of 12 years, 30 participants born with dense cataracts in both eyes who later had their vision surgically restored, 24 participants whose cataracts emerged before age 12 and were later removed, and 70 participants with normal vision.

The researchers presented all participants with four object pairs to be explored by touch. The objects in each pair were shapes that differed in their edges or surface patterns. Participants received the objects in an opaque cloth bag and were tasked with retrieving the object that best matched the sound of the pseudoword for that trial. Participants with visual capabilities additionally saw a fifth object pair and indicated which shape best matched the pseudoword.

Participants who experienced visual deprivation early in life performed no differently from chance level, regardless of whether they later had their vision restored, indicating that they did not have a systematic sound-shape association. The same was found in the group with a transient phase of visual impairments before the age of 12 (developmental cataract group). Only participants with late-onset blindness (after the age of 12) and participants with normal vision showed evidence of reliable sound-shape associations.

"Our data demonstrate two sides of sensitive periods: On the one hand, experience during an extended period of development is a prerequisite to acquire multisensory representations. On the other hand, representations acquired during this sensitive phase are not lost later in life despite dramatic and long-lasting changes in the environment," explains Sourav.

"Our data provide valuable information on the experience-dependent nature of multisensory processing, offering a starting point for asking questions about how our sensory modalities shape word formation and, ultimately, the languages we speak," Sourav concludes.

HOUSTON - (Sept. 9, 2019) - It only took the replacement of one atom for Rice University scientists to give new powers to biocompatible fluorescent molecules.

The Rice lab of chemist Han Xiao reported in the Journal of the American Chemical Society it has developed a single-atom switch to turn fluorescent dyes used in biological imaging on and off at will.

The technique will enable high-resolution imaging and dynamic tracking of biological processes in living cells, tissues and animals.

The Rice lab developed a minimally modified probe that can be triggered by a broad range of visible light. The patented process could replace existing photoactivatable fluorophores that may only be activated with ultraviolet light or require toxic chemicals to turn on the fluorescence, characteristics that limit their usefulness.

The researchers took advantage of a phenomenon known as photo-induced electron transfer (PET), which was already known to quench fluorescent signals.

They put fluorophores in cages of thiocarbonyl, the moeity responsible for quenching. With one-step organic synthesis, they replaced an oxygen atom in the cage with one of sulfur. That enabled them to induce the PET effect to quench fluorescence.

Triggering the complex again with visible light near the fluorescent molecule's preferred absorbance oxidized the cage in turn. That knocked out the sulfur and replaced it with an oxygen atom, restoring fluorescence.

"All it takes to make these is a little chemistry and one step," said Xiao, who joined Rice in 2017 with funding from the Cancer Prevention and Research Institute of Texas (CPRIT). "We demonstrated in the paper that it works the same for a range of fluorescent dyes. Basically, one reaction solves a lot of problems."

Researchers worldwide use fluorescent molecules to tag and track cells or elements within cells. Activating the tags with low-powered visible light rather than ultraviolet is much less damaging to the cells being studied, Xiao said, and makes the long exposures of living cells required by super-resolution imaging possible. Super-resolution experiments by Theodore Wensel, the Robert A. Welch Chair in Chemistry at Baylor College of Medicine, and his team confirmed their abilities, he said.

"We feel this will be a really good probe for living-cell imaging," Xiao said. "People also use photoactivatable dye to track the dynamics of proteins, to see where and how far and how fast they travel. Our work was to provide a simple, general way to generate this dye."

The researchers found their technique worked on a wide range of common fluorescent tags and could even be mixed for multicolor imaging of targeted molecules in a single cell.

Our global food production system uses 53 million tonnes of phosphate fertilizers annually, processed from 270 million tonnes of mined phosphate rock . Estimates show up to 90% phosphate loss from mine to fork . A considerable part of this loss is phosphate pollution in water, some of which creates "dead zones", areas where little or no marine life can survive. With an increase in food demand by 60% towards 2050 , our food production system will need even more phosphate fertilizers. But where do the fertilizers come from and where do they go?

UN estimates a population increase to 9 billion by 2050, correlated with a 60% increase in food demand. In a world where almost a billion people are undernourished and where we waste up to half of all food we produce, this will pose new challenges to our global food supply chain and production system. A key variable for food production is the supply of phosphate fertilizers, most of which come from the mining and processing of phosphate rock. Only a handful of countries produce and export phosphate rock and phosphate fertilizers in a phosphate market that is tending towards a Moroccan monopoly. The later stages of the supply chain also see up to 90% losses and the transformation of phosphorus from a valued resource into one of the main causes for eutrophication.

A new study conducted at Stockholm University and the University of Iceland shows that while Phosphorus is a key element to global food security, its supply chain is a black box. This can lead to social, political and environmental issues, which in turn can create phosphorus supply crises. The results are published in the article "Opening access to the black box: The need for reportingon the global phosphorus supply chain" in Ambio, A Journal of the Human Environment.

"Cradle-to-grave reporting along the phosphorus supply chain can reveal the untold story about the social, environmental, ethical and economic price we pay for the food we see on our supermarket shelves. It can also help countries - most of which are dependent on phosphate imports - tailor better policies to decrease the vulnerability of their agricultural sector" says Eduard Nedelciu, researcher at the Department of Physical Geography at Stockholm University and main author of the study.

The study, which is part of a larger European research project called Adaptation to a new Economic Reality (adaptecon.com) identifies four main challenges with reporting on phosphorus and phosphate fertilizers. First, terminologies and methodologies that are used to report on phosphate deposits are not harmonized and sometimes not transparent - this makes estimations of reserves and resources inaccurate and unreliable. Second, the phosphorus supply chain has up to 90% losses, which are poorly documented. Losses occur along all segments of the supply chain and this fragmentation of information makes it hard to accurately report on how much is lost and where. Better reporting could help design methods to decrease losses and increase efficiency. Third, there are environmental and social consequences occurring along the supply chain of phosphorus. For example, mining and processing phosphate rock is polluting water bodies and is dangerous to human health. Moreover, the phosphorus that leaks from agricultural land and sewage systems into the water can cause eutrophication and the so-called "dead-zones": areas in our oceans and seas where life cannot be supported anymore. But there is a social and ethical aspect to phosphorus too. Phosphate rock is increasingly mined from contested areas, such as Western Sahara, in what has been described by some as "illegal exploitation". Fourth, open access to data along the phosphorus supply chain is lacking. The authors reinforce the idea that public knowledge on phosphorus and its supply chain is necessary due to its direct link to food, a basic human right. Also, reporting on phosphorus can help better assess progress on a number of global indicators for sustainability, such as the Sustainable Development Goals.

Marie Schellens puts the study into perspective: "Phosphorus information is power. Reliable and regular data gathering can leverage corporate social responsibility as well as political action. Both are needed to tackle many of the issues identified along the supply chain. Transparency can foster a sustainable and socially just supply chain for decades to come."

Epidemiological studies rely heavily on survey research; however, limitations of traditional data collection methods - paper-based, in-person, phone, mail, and internet surveys - can serve as barriers to recruitment and retention of research participants. Conventional data collection methods are especially ineffective for aging minority populations, who may have limited English proficiency and less access to and facility with technology. To overcome these research barriers, Rutgers researchers developed an adaptable web-based platform to facilitate in-person, multilingual survey data collection with minority research participants.

The platform, in use since 2011 for the PINE Study, or the Population Study of Chinese Elderly, a longitudinal cohort study of more than 3,000 older Chinese Americans, is the focus of a new article in the Journal of the American Geriatrics Society.

"The custom web application allows our researchers to administer in-person interviews in a study participant's preferred language and dialect," said study author XinQi Dong, director of Rutgers University's Institute for Health, Health Care Policy and Aging Research and the lead researcher of The PINE Study. "This method of data collection has allowed our researchers to overcome common cultural and communication barriers and has promoted the development of stronger interpersonal connections between researchers and participants."

The application allows for surveys to be administered in-home via a wireless device by trained multilingual and bicultural research assistants in participants' preferred language or Chinese dialects. The application then transmits the data through wireless services to a secure server in real-time.

Once data is entered into the database, multiple features are enabled to optimize quality monitoring, data security, and streamlined data set preparation for analysis purposes. Additional enhanced security measures ensure data safety and security of participant information.

According to Dong, the application allows research staff to actively engage with the participants during the survey process to develop rapport and ensure comprehension.

"Administering the surveys on mobile devices allows for greater eye contact and facilitates the generation of a more organic conversation between researcher and participant," he said. "These interactions foster stronger interpersonal connections among study participants and our researchers. This has led to improved participation and retention rates, with a respective 89.4 and 90.4 percent of participants completing follow-up interviews in the second and third research waves."

Dong said the application could potentially serve as a guide to aid population health researchers in the design and implementation of digital survey platforms to facilitate large-scale epidemiological studies with minority older adults.

"This innovative platform addresses multiple challenges related to collecting data in minority and vulnerable populations," Dong said. "With advantages such as real-time data quality monitoring and programmed automatic data validation, multilingual interface, streamlined data set preparation, and automatic built-in skip patterns to reduce interviewer errors, this application has the potential to revolutionize survey research and ultimately improve the health and well-being of many diverse populations."

CHAMPAIGN, Ill. -- If you want something done, ask a busy person - or so the saying goes. According to a new paper co-written by a University of Illinois scholar who studies attitudes and persuasion psychology, if you want to sell something quickly, it helps to try a busy consumer.

People on a tight deadline have stronger intentions to enact behaviors - whether it's redeeming a coupon or following through on receiving a flu shot - immediately after moving than after sitting, says research co-written by Dolores Albarracin, a professor of psychology and marketing at Illinois and the director of the Social Action Lab.

Movement - whether it's walking or running - is associated with action-oriented concepts and goals, whereas stasis - standing or sitting, for example - is associated with inaction-oriented concepts and goals.

Across one field experiment and three lab experiments, Albarracin and co-author Duo Jiang, a graduate student at Illinois, found that prior movement was associated with a higher probability of enacting behaviors while under a tight deadline.

Consider two people - one walking, the other sitting - who each face the decision of whether to go to a pharmacy for a flu shot.

"What we found is that walking involves activating action representations that in turn promote other actions outside of the context of walking," Albarracin said. "Likewise, sitting involves activating inaction representations that may promote inaction outside of the context of sitting. These general goals of action and inaction are likely to be broad enough to guide decisions about the flu shot: The person who's in motion will get the flu shot, and the person who's inactive won't."

The reason for this is that when you're in a hurry and you're under a close deadline, "both being in a hurry and having the deadline push in the same direction of completing the transaction as quickly as possible," Albarracin said.

"You're thinking, 'I can make this deadline,' and you can make it when you have thoughts about being active and energetic. Likewise, sitting involves rest and relaxation, which promotes more general inactivity and transfers to any behavior relevant in the moment."

The concepts and goals, whether they're action- or inaction-focused, can transfer to any task at hand, Albarracin said.

"If the task is a purchase, people are more willing to complete the purchase," she said. "But the goals elicited by movement affect decisions that need to be made immediately. So someone walking around a park is more likely to complete a deadline-driven purchase than someone sitting on a park bench contemplating life. But walking or sitting would not affect decisions about future purchases."

The research has implications for marketing and advertising, said Albarracin, also a professor of business administration with the Gies College of Business.
"If there's a deadline to buy a product or service and there's someone who's more action-oriented versus someone who's more static, you want to give the action people a tight deadline, because they'll respond really quickly, whereas the more sedentary people will just say, 'Eh, whatever,'" she said.

These findings also might extend to the types of products you're trying to sell, Albarracin said.

"If you're trying to sell a product with a very short shelf life, like food or coffee, you can use movement to your advantage," she said. "You give people a really tight window to purchase the product, and the more action-oriented people - who also are perhaps users of mobile technology - are going to snap it up. If you're selling something like athletic wear, for example, a close deadline would work better. But if you have a product that has a longer shelf life, like a car or a computer, whether your audience moves or uses mobile technology for consumer decisions may not matter."

Tel Aviv University and Sheba Medical Center researchers say they have discovered why more than half of patients with metastatic melanoma do not respond to immunotherapy cancer treatments.

Wielding proteomics, an innovative "protein mapping" approach, a team of researchers led by Prof. Tami Geiger, Prof. Gal Markel, and Dr. Michal Harel of TAU's Sackler School of Medicine and Sheba's Ella Lemelbaum Institute for Immuno-Oncology have answered the burning question: Why do immunotherapy treatments greatly help some patients with melanoma but not affect 60 percent of metastatic melanoma patients?

The researchers, whose findings were published on September 5 in Cell, compared the responses of 116 melanoma patients to immunotherapy -- one group in which immunotherapy was successful and a second in which immunotherapy was not successful. Harnessing proteomics, a powerful protein mapping technology, they discovered differences in the metabolism, or energy production process, of the cancer cells of the two groups.

"In recent years, a variety of cancer immunotherapy therapies have been used, therapies that strengthen the anti-cancer activity of the immune system," explains Prof. Markel, a senior oncologist and scientific director of the Ella Lemelbaum Institute. "These treatments have been shown to be highly effective for some patients and have revolutionized oncology. However, many patients do not respond to immunotherapy, and it is critical to understand why.

"Can we predict who will respond? Can we alter treatment in order to increase responses? In our research, we focused on metastatic melanoma, a devastating disease that until recently had no efficient treatments. It was clear to us that pre-treatment samples from responders and non-responders would be key."

To better understand treatment resistance mechanisms, the scientists examined tumors taken from 116 patients using proteomics.

"In the proteomic lab, we use an instrument called a mass-spectrometer, which enables global mapping of thousands of proteins," explains Prof. Geiger, head of TAU's Proteomics Lab. "We then followed up with extensive computational analysis to identify the proteins that differentiated between the response groups."

The proteomic comparison identified major differences between responders and non-responders to immunotherapy. "In the responders, we found higher levels of proteins associated with lipid metabolism, which led to better recognition by the immune system," says Prof. Geiger.

In collaboration with the Salk Institute in San Diego and Yale School of Medicine, researchers then examined their findings in melanoma tissue cultures and a mouse model of metastatic melanoma.

Using genetic engineering, they were able to silence the mechanism responsible for fatty acid metabolism.

"We found that upon silencing this metabolic pathway, the cancer cells manage to 'hide' from T-cells that are supposed to detect and destroy them," says Prof. Geiger. "As a result, cancer in these mice developed at a faster rate compared to the control group.

"In our study, we identified a significant difference between melanoma patients who live for years thanks to immunotherapy, and patients who are not at all affected by the treatment."

"These findings can also be relevant to many other malignancies," adds Prof. Markel. "Now, in subsequent studies, we are looking for ways to improve the response to immunotherapy and expand the circle of patients who benefit from it. In addition, we are looking for a method that will allow clinicians to anticipate which patients will respond to treatments."

Scientists from the School of Medicine, Trinity College Dublin, have, for the first time, discovered a family of proteins that are associated with lower blood sugar levels among obese patients with type 2 diabetes.

Their research is published today (Monday, September 9th, 2019) in the international journal Nature Communications here: https://rdcu.be/bQlWW. The study showed that patients with type 2 diabetes who have high levels of the protein, IL-36 cytokines, were found to have lower blood sugar levels, implying that those proteins are associated with better control of the patient's blood sugar levels and their disease.

IL-36 cytokines are members of a larger family of proteins known as the interleukin-1 family which have emerged as central players in the development of obesity related disease.

Researchers have linked the protective effects of these proteins with their ability to alter the make-up of the intestinal microbiome.

Obesity causes an increased level of fatty acids and inflammation leading to insulin resistance. When the body is resistant to the insulin it produces it causes a high build-up of glucose or blood sugar, ultimately leading to type 2 diabetes.

Obesity is now recognised as a global pandemic and has been definitively linked to a wide range of diseases including metabolic disorders such as diabetes, stroke and many types of cancer. The World Health Organisation state that global levels of obesity have more than doubled since 1980. In Ireland, according to the Healthy Ireland survey, 854,165 adults over 40 in the Republic of Ireland are at increased risk of developing (or have) type 2 diabetes. The economic burden of diabetes on the Irish health care system is becoming a major challenge for the government.

Given the scale and global reach of the problem, current approaches aimed at reversing the tide of obesity driven disease are insufficient. The Trinity research team believe that there is an urgent need to achieve a greater understanding of the mechanisms associated with obesity related diseases.

Lead scientist Dr Patrick Walsh from the School of Medicine, Trinity, said: "This study has added to a substantial body of work which has revealed the important function of the broader interleukin-1 family as mediators of metabolic health and disease. Our findings have opened the door to a deeper investigation of how IL-36 cytokines impact on the development of such diseases in humans and whether this can be exploited for the better treatment of patients."