Brain

Vertebrate, insect, and plant cell lines are important tools for research in many disciplines, including human health, evolutionary and developmental biology, agriculture and toxicology. Cell lines have been established for many organisms, including freshwater and terrestrial invertebrates.

Despite many efforts over multiple decades, there are still no cell lines for marine invertebrates including marine sponges, which are the source of thousands of novel chemicals with pharmaceutically relevant properties. Supply of these chemicals also is a bottleneck to development of sponge-derived drug leads, because wild harvest is not ecologically sustainable, and chemical synthesis is challenging due to the complexity of many of the bioactive chemical compounds.

Researchers from Florida Atlantic University's Harbor Branch Oceanographic Institute and collaborators at Wageningen University in the Netherlands have developed a breakthrough in marine invertebrate (sponge) cell culture. For the first time, they have accomplished a substantial increase in both the rate and number of cell divisions. They have demonstrated that an amino acid-optimized nutrient medium stimulates rapid cell division in nine marine sponge species. The demonstration of exceptionally fast cell division for marine invertebrates (sponges), as well as the researchers' ability to subculture the cells, is a groundbreaking discovery for marine biotechnology.

Results of the study, published in Scientific Reports, showed that the fastest dividing cells doubled in less than one hour. Cultures of three species were subcultured from three to five times, with an average of 5.99 population doublings after subculturing, and a lifespan from 21 to 35 days.

These findings form the basis for developing marine invertebrate cell models to better understand early animal evolution, determine the role of secondary metabolites, and predict the impact of climate change to coral reef community ecology. Furthermore, sponge cell lines can be used to scale-up production of sponge-derived chemicals for clinical trials and to develop new drugs to combat cancer and other diseases.

"Sponge cell lines could be used as models to understand the role of secondary metabolites in sponges, to use this information to develop new models for drug discovery, and to scale-up production of sponge-derived bioactive compounds for novel medicines," said Shirley Pomponi, Ph.D., senior author and a research professor at FAU's Harbor Branch. "Cell lines of common reef sponges also could be used to quantify the effects of climate change such as ocean warming and acidification on uptake of dissolved organic material, a major component of the 'sponge loop hypothesis' of carbon cycling, and to test the hypothesis that coral reefs could become sponge reefs as climate changes."

Sponges (Phylum Porifera) are among the oldest Metazoa and considered critical to understanding animal evolution and development. They are key components of many benthic marine ecosystems. There are more than 9,000 described species that occur worldwide, from the intertidal to the deep sea. Among the oldest metazoans, sponges have evolved a variety of strategies to adapt to different environments. Because they are sessile as adults, they have evolved sophisticated chemical systems for communication, defense from predators, antifoulants to prevent other organisms from growing over them, and to prevent infection from microbes filtered out of the water. These chemicals interact with molecules that have been conserved throughout evolutionary history and are involved in human disease processes, for example, cell cycling, immune and inflammatory responses, and calcium and sodium regulation.

For years, scientists at FAU's Harbor Branch have been collecting unusual marine organisms -- many of them from deep-water habitats -- that are the source of novel natural products. The majority of samples come primarily from around the Atlantic and Caribbean; others have come from the Galapagos, western Pacific, Mediterranean, Indo-Pacific, Western Africa and the Bering Sea. FAU Harbor Branch's drug discovery program looks for treatments for pancreatic cancer and infectious diseases, and their scientists also have collaborations with other scientists working on other forms of cancer, malaria, tuberculosis, neurodegenerative disease and inflammation.

Most images captured by a camera lens are flat and two dimensional. Increasingly, 3D imaging technologies are providing the crucial context of depth for scientific and medical applications. 4D imaging, which adds information on light polarization, could open up even more possibilities, but usually the equipment is bulky, expensive and complicated. Now, researchers reporting in ACS Nano have developed self-assembling liquid crystal microlenses that can reveal 4D information in one snapshot.

Polarized light contains waves that undulate in a single plane, whereas unpolarized light, such as that from the sun, contains waves that move in every direction. Light can become polarized by reflecting off objects, and detecting this type of light could reveal hidden information. For example, cancer cells can reflect polarized light differently than healthy tissues. Wei Hu, Yan-Qing Lu and colleagues wanted to develop a portable, inexpensive and easy-to-use microlens to simultaneously acquire 3D space and polarization information, thereby producing 4D images.

To make their microlenses, the researchers used liquid crystals, materials found in most electronic displays. With a self-assembly process, they patterned arrays of liquid crystal microlenses into concentric circles. The researchers used a polarized optical microscope to image objects, such as a cross or the letter "E," under different directions of linearly polarized light. Microlenses in the array imaged the object differently, depending on their distance from the object (depth) and the direction of polarized light, producing 4D information. Although the resolution needs to be improved, the technique could someday be used in applications such as medical imaging, communications, displays, information encryption and remote sensing, the researchers say.

Plants get stressed too. Environmental factors such as drought or a high concentration of salt in the soil disrupt their physiology. All land plants, from liverwort to rye, use a complex signalling cascade under stressful conditions. An international research team led by the Hebrew University of Jerusalem with the participation of the University of Göttingen investigated how evolutionary changes in receptor proteins led to their ability to sense the plant hormone abscisic acid (ABA). This enabled them to develop sensing mechanisms that aided their colonization of dry land and their response to stress conditions. The results were published in the journal Proceedings of the National Academy of Sciences (PNAS).

The signalling cascade of stress in "land plants", ie all plants that grow on land from moss to trees but not algae, is based on the detection of the messenger substance abscisic acid, which is a plant hormone. According to scientific understanding, this hormone's action has long been regarded as a key characteristic of land plants. Scientists suspected that this hormone, which regulates stress responses, helped plants early on in their evolution to cope with the stress they were exposed to during the "conquest" of the land.

Co-author Professor Jan de Vries from the Institute of Microbiology and Genetics at the University of Göttingen says: "We were able to show that the closest living algae relatives of land plants, the zygnematophyceaen green algae (to some unflatteringly known as 'pond scum'), have a complete set of genes that strongly resembles the genetic framework that land plants use for the detection of abscisic acid. In particular, we found that the first step in the signalling cascade was present: a possible receptor for the hormone."

In the current study, an international team consisting of researchers from four different countries and led by the Hebrew University of Jerusalem, investigated whether and how this receptor gene integrates into the signalling cascade. "Using molecular biological methods, we found out that it integrates into the signalling cascade and is able to regulate it," says de Vries. "However, it does this independently of the hormone abscisic acid."

In land plants, the signalling cascade hinges on the action of the stress hormone. However, algae do not use the hormone as a trigger for the signalling cascade -- so the cascade has an origin independent from this function as hormone-dependent signalling framework. Interestingly, this original mechanism still functions in land plants - in addition to the well-known hormone-dependent mechanism that every biology student learns.

An international group of scientists with IKBFU professor Anatoliy Snigirev among them has published an article that proposes a new method for studying the structure of complexly organized materials of both artificial and natural origin. The article was published by the Journal of Applied Crystallography.

Prof. Anatoliy Snigirev said:

"After the discovery of x-ray radiation, it became possible to study the structure of natural crystals, because the wavelength of the x-ray beam is proportional to the interatomic distance of rigid bodies. But there are many self-organizing three-dimensional materials - both of natural and artificial origin, which are difficult to study using x-rays, since the distance between trace elements - "atoms" is 100 and 1000 times greater. In the published work, we proposed using special X-ray lenses to study such structures, which, refracting the light in a certain way, make it possible to see the diffraction pattern, and based on it draw a conclusion about the internal structure of the material "

It should be clarified that Anatoly Snigirev, together with his colleagues, developed X-ray lenses back in 1996. But they could only become truly effective recently, when powerful 3rd generation synchrotrons (resonant cyclic electron accelerators that move in a circular orbit) appeared with which they can be used.

According to the scientist, the possibility of a thorough study of self-organizing materials can revolutionize many industries.

As for the scope of self-organizing structures, it is incredibly wide. And the hopes for these materials are very high. For example, it is assumed that photonic crystals grown by humans, replacing silicon, will revolutionize electronics by making a variety of optoelectronic devices and, in particular, computers, many times faster and more powerful.

The method of studying self-organizing materials proposed by scientists can be useful to biologists studying the structure of tissues of living organisms - for example, corals or insect shells.

According to Anatoly Snigirev, a team of scientists representing different fields of knowledge, that has developed a new method for studying self-organizing materials, has been involved in a large-scale project to create a new fourth-generation synchrotron. This project, called SKIF, will be implemented in Novosibirsk.

After a decade-long search, an international team of researchers including the Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU) have for the first time detected a gamma-ray burst in very-high-energy gamma light. This discovery was made in July 2018 by the H.E.S.S. collaboration using the huge 28-m telescope of the H.E.S.S. array in Namibia. Surprisingly, this Gamma-ray burst, an extremely energetic flash following a cosmological cataclysm, was found to emit very-high-energy gamma-rays long after the initial explosion.

Extremely energetic cosmic explosions generate gamma-ray bursts (GRB), typically lasting for only a few tens of seconds. They are the most luminous explosions in the universe. The burst is followed by a longer lasting afterglow mostly in the optical and X-ray spectral regions whose intensity decreases rapidly. The prompt high energy gamma-ray emission is mostly composed of photons several hundred-thousands to millions of times more energetic than visible light, that can only be observed by satellite-based instruments. Whilst these space-borne observatories have detected a few photons with even higher energies, the question if very-high-energy (VHE) gamma radiation (at least 100 billion times more energetic than visible light and only detectable with ground-based telescopes) is emitted, has remained unanswered until now.

On 20 July 2018, the Fermi Gamma-Ray Burst Monitor and a few seconds later the Swift Burst Alert Telescope notified the world of a gamma-ray burst, GRB 180720B. Immediately after the alert, several observatories turned to look at this position in the sky. For H.E.S.S. (High Energy Stereoscopic System), this location became visible only 10 hours later. Nevertheless, the H.E.S.S. team decided to search for a very-high-energy afterglow of the burst. After having looked for a very-high-energy signature of these events for more than a decade, the efforts by the collaboration now bore fruit.

A signature has now been detected with the large H.E.S.S. telescope that is especially suited for such observations. The data collected during two hours from 10 to 12 hours after the gamma-ray burst showed a new point-like gamma-ray source at the position of the burst. While the detection of GRBs at these very-high-energies had long been anticipated, the discovery many hours after the initial event, deep in the afterglow phase, came as a real surprise. The discovery of the first GRB to be detected at such very-high-photon energies is reported in a publication by the H.E.S.S. collaboration et al., in the journal Nature on November 20.

H.E.S.S. is an international collaboration involving scientists from 13 countries, including Kavli IPMU Principal Investigator Tadayuki Takahashi and Rikkyo Univeristy Professor Yasunobu Uchiyama.

GRB 180720B was very strong and lasted for about 50 seconds - a relatively long duration indicating the death of a massive star. In this process, its core collapses to a rapidly rotating black hole. The surrounding gas forms an accretion disk around the black hole, with gas jets ejected perpendicularly to the disk plane creating the gamma-ray flashes. Elementary particles are accelerated in these jets to velocities nearly as high as the speed of light and interact with the surrounding matter and radiation, leading to the copious production of gamma rays.

The very-high-energy gamma radiation which has now been detected not only demonstrates the presence of extremely accelerated particles in GRBs, but also shows that these particles still exist or are created a long time after the explosion. Most probably, the shock wave of the explosion acts here as the cosmic accelerator. Before this H.E.S.S. observation, it had been assumed that such bursts likely are observable only within the first seconds and minutes at these extreme energies, and not many hours after the explosion.

At the time of the H.E.S.S. measurements the X-ray afterglow had already decayed very considerably. Remarkably, the intensities and spectral shapes are similar in the X-ray and gamma-ray regions. There are several theoretical mechanisms for the generation of very-high-energy gamma light by particles accelerated to very-high-energies. The H.E.S.S results strongly constrain the emission to two potential mechanisms. In both cases, however, the observations raise new questions. "Although energetically one of these mechanisms is preferred, both the shape of the H.E.S.S. spectrum, and the energy range of the emission at such late times presents a challenge to both emission scenarios." - says H.E.S.S. scientist Andrew Taylor.

This breakthrough discovery provides new insights into the nature of gamma-ray bursts. As highlighted by Edna Ruiz Velasco, PhD. student at MPIK in Heidelberg and one of the corresponding authors of the publication: "This detection has already revolutionised the way we search for GRBs with Cherenkov Telescopes. Thanks to this GRB and the lessons learnt, our recently improved observational strategy has already payed off. We can expect a future with a great number of GRBs detections at very-high energies and with this, a deeper understanding of these phenomena".

UPTON, NY--Scientists have developed a new approach for making metal-metal composites and porous metals with a 3-D interconnected "bicontinuous" structure in thin films at size scales ranging from tens of nanometers to microns. Metallic materials with this sponge-like morphology--characterized by two coexisting phases that form interpenetrating networks continuing over space--could be useful in catalysis, energy generation and storage, and biomedical sensing. Called thin-film solid-state interfacial dealloying (SSID), the approach uses heat to drive a self-organizing process in which metals mix or de-mix to form a new structure. The scientists used multiple electron- and x-ray-based techniques ("multimodal analysis") to visualize and characterize the formation of the bicontinuous structure.

"Heating gives the metals some energy so that they can interdiffuse and form a self-supported thermodynamically stable structure," explained Karen Chen-Wiegart, an assistant professor in Stony Brook University's (SBU) Materials Science and Chemical Engineering Department, where she leads the Chen-Wiegart Research Group, and a scientist at the National Synchrotron Light Source II (NSLS-II)--a U.S. Department of Energy (DOE) Office of Science User Facility at Brookhaven National Laboratory. "SSID has been previously demonstrated in bulk samples (tens of microns and thicker) but results in a size gradient, with a larger structure on one side of the sample and a smaller structure on the other side. Here, for the first time, we successfully demonstrated SSID in a fully integrated thin-film processing, resulting in a homogenous size distribution across the sample. This homogeneity is needed to create functional nanostructures."

Chen-Wiegart is the corresponding author on a paper published online in Materials Horizons that is featured on the Nov. 18 online journal issue cover. The other collaborating institutions are the Center for Functional Nanomaterials (CFN)--another DOE Office of Science User Facility at Brookhaven Lab--and the National Institute of Standards and Technology (NIST).

To demonstrate their process, the scientists prepared magnesium (Mg) and iron (Fe) and nickel (Ni) alloy thin films on silicon (Si) wafer substrates in the CFN Nanofabrication Facility. They heated the samples to high temperature (860 degrees Fahrenheit) for 30 minutes and then rapidly cooled them down to room temperature.

"We found that Mg diffuses into the Fe-Ni layer, where it combines only with Ni, while Fe separates from Ni," said first author Chonghang Zhao, a PhD student in the Chen-Wiegart Research Group. "This phase separation is based on enthalpy, an energy measurement that determines whether the materials are "happily" mixing or not, depending on properties such as their crystal structure and bonding configurations. The nanocomposite can be further treated to generate a nanoporous structure through chemically removing one of the phases."

Nanoporous structures have many applications, including photocatalysis. For example, these structures could be used to accelerate the reaction in which water is split into oxygen and hydrogen--a clean-burning fuel. Because catalytic reactions happen on material surfaces, the high surface area of the pores would improve reaction efficiency. In addition, because the nanosized "ligaments" are inherently interconnected, they do not need any support to hold them together. These connections could provide electrically conductive pathways.

The team identified the dealloyed bicontinuous structure of Fe and Ni-Mg through complementary electron microscopy techniques at the CFN and x-ray synchrotron techniques at two NSLS-II beamlines: the Hard X-ray Nanoprobe (HXN) and Beamline for Materials Measurement (BMM).

"Using the scanning mode in a transmission electron microscope (TEM), we rastered the electron beam over the sample in specific locations to generate 2-D elemental maps showing the spatial distribution of elements," explained Kim Kisslinger, a technical associate in the CFN Electron Microscopy research group and the point of contact for the instrument.

The team also used TEM to obtain electron diffraction patterns capturing the crystal structure and a scanning electron microscope (SEM) to study surface morphology.

This initial analysis provided evidence of the formation of a bicontinuous structure locally in 2-D at high resolution. To further confirm that the bicontinuous structure was representative of the entire sample, the team turned to HXN beamline, which can provide 3-D information over a much larger region.

"With HXN, we can focus hard, or high-energy, x-rays to a very tiny spot of about 12 nanometers," said coauthor and HXN physicist Xiaojing Huang. "The world-leading spatial resolution of hard x-ray microscopy at HXN is sufficient to see the sample's smallest structures, which range in size from 20 to 30 nanometers. Though TEM provides higher resolution, the field of view is limited. With the x-ray microscope, we were able to observe the 3-D element distributions within a bigger area so that we could confirm the homogeneity."

Measurements at HXN were conducted in a multimodality manner, with the simultaneous collection of x-ray scattering signals that reveal 3-D structure and fluorescence signals that are element-sensitive. Atoms emit fluorescence when they jump back to their lowest-energy (ground) state after being excited to an unstable higher-energy state in response to the x-ray energy. By detecting this characteristic fluorescence, scientists can determine the type and relative abundance of elements present at specific locations.

Coauthor and NIST Synchrotron Science Group physicist Bruce Ravel confirmed the sample's chemical composition and obtained the precise chemical forms (oxidation states) of the elements at BMM, which is funded and operated by NIST. The x-ray absorption near-edge structure (XANES) spectra also showed the presence of pure Fe.

Now that the scientists have shown that SSID works in thin films, their next step is to address the "parasitic" events they identified in the course of this study. For example, they discovered that Ni diffuses into the Si substrate, leading to voids, a kind of structural defect. They will also make pore structures from the metal-metal composites to demonstrate applications such as photocatalysis, and apply their approach to other metal systems, including titanium-based ones.

Hartford, Conn. -- Seventy percent of teens surveyed report engaging with food and beverage brands on social media and 35 percent engaged with at least five brands, according to a new study from the UConn Rudd Center for Food Policy & Obesity published in the journal Appetite. The study, funded by the Robert Wood Johnson Foundation, found that 93 percent of the brands that teens reported engaging with on social media were fast food, unhealthy snack foods, candy, and sugary drinks, which are primarily the brands that target them with traditional forms of advertising.

The study surveyed 1,564 U.S. teens ages 13-17 about their engagement (liking, sharing, or following) with food and beverage brands on social media, such as Facebook, Instagram, YouTube, and Snapchat, their time spent watching TV and on other screens (e.g., cell phones, computers), and demographic characteristics. The survey was conducted from March to May of 2017.

Study authors say the findings reflect how food and beverage companies use social media to reach teens. Almost 40 percent of teens surveyed for the study reported being on other screens (non-TV) 4 or more hours each day, where social media dominates their time. Social media marketing comes in the form of attention-getting videos and other posts on companies' social media accounts designed to create engagement (comments, likes, shares, follows) that encourages teens to essentially market these products to friends in their social networks.

"This study shows how successful companies are at using social media to reach teens and take advantage of teens' peer networks. Companies usually pay big bucks to market their brands, but with social media they are getting teens to do it for free. And, since teens' choices are heavily influenced by their peers, the payoff is huge," said Fran Fleming-Milici, PhD, lead study author and assistant research professor for the Rudd Center. "Parents don't realize that all of their efforts to create a healthy food environment at home are undermined when their kids are bombarded by unhealthy food marketing on their phones and computer screens."

The study also found that brand engagement was highest among Black teens, Spanish-speaking Hispanic teens, and teens whose parents have lower education levels. These findings raise public health concerns due to higher rates of diet-related diseases among communities of color. Authors say more research is needed to fully understand why brand engagement was higher among these groups, but another Rudd Center report found that food companies disproportionately target Black and Hispanic youth with advertising for many of the same unhealthy brands that teens report engaging with the most on social media.

Other key findings:

Of teens surveyed, those who watched 2 or more hours of TV a day were much more likely to engage with at least one fast food, sugary drink, candy, or snack brand on social media than teens who watched less than 2 hours per day.

A few brands dominated teens' social media engagement, including Doritos, Coke, Pepsi, Hershey, Snickers, and McDonald's. More than one-third of teens who said they liked, shared, or followed fast food, sugary drink, candy, or snack brands engaged with these specific brands.

Younger teens (age 13-14) in the study engaged with brands as frequently as older teens (age 15-17) on social media despite spending 30 minutes less each day using other screens (not TV) than older teens. TV viewing times did not differ between age groups.

"It's probably not a coincidence that the brands that teens engage with the most on social media are the same ones that spend the most to target them with advertising messages designed to make their products seem fun, cool, and daring," said Jennifer L. Harris, PhD, MBA, study author and director of Marketing Initiatives at the Rudd Center. "Unfortunately, those products also have high amounts of added sugars, fat, and calories that can lead to negative health consequences for a lifetime."

Researchers recommend that food and beverage manufacturers stop targeting teens with marketing for products that can harm their health. Currently, the food and beverage companies' voluntary self-regulatory program, the Children's Food and Beverage Advertising Initiative, only limits unhealthy advertising to children up to 11 years old.

Researchers say the program should cover children up to at least 14 years old.

Study authors also recommend that more states and localities enact excise taxes on sugary drinks to increase the cost of unhealthy beverages to help reduce teens' consumption. Companies must also stop disproportionately targeting marketing of their least healthy products to teens in communities of color.

If you've ever woken up in the middle of the night to go to the bathroom and stumbled around in the dark, banging into walls or dressers in a room you've walked through countless times, you've experienced the effects of inadequately calibrated neurons.

In many animals, humans included, an accurate sense of direction is generated with the help of brain cells known as head direction neurons, which do so by incorporating two main streams of information--visual landmarks and positional estimates based on self-movement.

Without the former, our ability to navigate even familiar locations degrades. But given a visual landmark--like the glow of an alarm clock or the shadow of a door--our internal map of the environment refreshes, and we can make our way with ease once again.

A similar process occurs in fruit flies, which use so-called compass neurons to keep track of the orientation of their heads and body. In a new study, published in Nature on Nov. 20, Harvard Medical School neuroscientists have now decoded how visual cues can rapidly reorganize the activity of these compass neurons to maintain an accurate sense of direction.

By tracking individual neurons in fruit flies as they navigate a virtual reality environment, the researchers shed light on neural mechanisms that allow organisms to build a spatial map of their world, as well as processes involved in short-term memory.

"When we look at the pattern of connections between compass neurons and the visual system, we see that they are remodeled by visual experiences," said senior study author Rachel Wilson, the Martin Family Professor of Basic Research in the Field of Neurobiology in the Blavatnik Institute at HMS.

"These changes are happening over minutes and correspond with the timescale that we experience subjectively when we enter a new environment and explore it," Wilson said. "To me, it's remarkable that we can get insight into something as complicated as spatial navigation by studying a brain that's smaller than a poppy seed."

Virtual sun

Comprised of only around 100,000 neurons, the Drosophila fruit fly brain is capable of highly complex behaviors. Previous studies have shown that during navigation, compass neurons, also known as E-PG neurons, are critical for the fly's ability to sense direction.

These neurons are arranged into a ring, like the dial of a compass. As the fly moves, a corresponding "bump" of neural activity moves around the ring like a compass needle--if the fly turns 90 degrees, the bump of activity also rotates 90 degrees.

In the dark, the accuracy of this "needle" diminishes due to the absence of visual clues, as the organism only has estimates of its own movements to navigate with. But given a visual prompt, the needle snaps back to place, accurately reflecting the fly's heading.

To investigate how visual inputs alter this process, Wilson and team--including lead study author Yvette Fisher, research fellow in neurobiology; Jenny Lu, an MD/PhD student; and Isabel D'Alessandro, a research assistant--carried out a series of experiments that combined virtual reality with high-powered microscopy.

They fixed a fly to a pin with glue and lowered it onto a Styrofoam ball floating frictionless on a column of air. Surrounded by a visual panorama, the fly moved its legs to walk and turn, causing the ball to rotate and giving precise measurements of the fly's movements. An imaging technique known as two-photon microscopy allowed the researchers to visualize the activity of individual neurons in the fly's brain as it navigated in virtual reality.

Flies were presented with a visual cue--an unapproachable bright point of light that served to represent the sun, which insects use for long-distance navigation.

Initially, flies would try to approach the virtual sun. After some time, they would walk in a straight line at a fixed angle to the sun; and if the light moved, the flies made a compensatory turn to return to that fixed angle, demonstrating that they were paying attention to the virtual object and using it for course control.

When the team looked in the fly brain, they found that the activity of compass neurons was being influenced by visual system-associated neurons, known as R neurons. Specifically, R neurons were inhibiting compass neuron activity in a spatially specific manner, thereby reorienting the compass.

"Basically, visual system inputs seem to push the compass needle, so to speak, to the part of the compass that isn't being inhibited," Wilson said. "This will push the compass away from the wrong direction toward the right direction."

Plastic memory

After the flies were acclimated, the researchers presented them with a second virtual sun, directly opposite of the first. This caused the activity of compass neurons to occasionally flip around 180 degrees.

When the second sun was removed, compass activity was variable--sometimes it would settle down into its original heading, sometimes the opposite, and sometimes, it would continue to swing around back and forth.

"It's as if the fly became confused or was changing its mind about what direction it was pointed in," Wilson said.

The researchers found that this process depended on the interaction of compass neurons and R neurons, specifically the strength of inhibitory activity at the synapses, or points of connection, between them. Inputs from the visual system can reshape the function of those connections over the timespan of a few minutes.

Thus, a visual cue can interact with the representation of direction contained within compass neurons and alter their activity to remodel the compass, ultimately changing the fly's sense of direction.

"The exciting thing for us is that the pattern of inhibitory inputs from visual neurons onto compass neurons is plastic," Wilson said. "We can reorganize that functional pattern by just giving the fly an altered experience in virtual reality."

This is likely relatable to mammals and other organisms, she added. "When navigating in a new environment, it often feels like it takes a few minutes to build up a mental map of the neighborhood or park or office you walked into. That's the timescale in which these changes in synapse strength are occurring."

Their findings now provide a mechanistic explanation for how visual experiences can directly alter the activity of direction-sensing neurons to change how the brain maps its internal representation of the world.

A better understanding of this process also sheds light on a form of short-term learning known as unsupervised learning, in which the brain aims to be as consistent with itself and its environment as possible, without the influence of reward or punishment.

"Short-term memory is encoded in the ring. If you turn off the lights, it retains a memory of the direction its headed," Wilson said. "You can watch that memory evolve as the fly tracks the turns it makes and integrates those movements over time to update the compass. You can also watch that memory slowly become more inaccurate over time."

"When you turn the lights back on, the compass clicks back into the right answer. We've all had that experience, I think, where you can catch sight of a visual landmark and feel the compass in your brain sort of rotate, and then you just see the world differently," she continued. "We can watch those dynamics here in the fly brain, in real time."

An international, multidisciplinary research team from more than 50 institutions, led by geneticist and psychiatrist Gholson Lyon, MD, PhD, of the New York State Office for People With Developmental Disabilities' (OPWDD) Institute for Basic Research in Developmental Disabilities (IBR), today announced publication of findings from its study of the rare disease TAF1 syndrome.

The findings were published in the article "Missense variants in TAF1 and developmental phenotypes: challenges of determining pathogenicity," in Human Mutation, the official journal of the Human Genome Variation Society, published by John Wiley Press.

People with TAF1 syndrome present early in life with hypotonia, facial dysmorphia, and developmental delay that evolves into intellectual disability and/or autism spectrum disorder.

Dr. Lyon and his research team previously described a new neurodevelopmental syndrome, TAF1/MRXS33 intellectual disability syndrome, which is caused by pathogenic variants involving the X-linked gene TAF1. In the earlier study, the group identified 11 families from around the world with the syndrome.

In this recent study, sponsored by OPWDD, the researchers identified an additional 27 families with the syndrome by using a 'genotype first approach', which clusters families based on mutations in the same gene, followed by detailed clinical analysis of those families. The study integrates results from many disciplines and presents a novel phenotypic clustering in which the phenotypes, or observable physical characteristics, of affected individuals were classified by using 51 standardized clinical descriptions, referred to as Human Phenotype Ontology (HPO) terms. Phenotypes associated with TAF1 variants show considerable clinical variability, but prominent among the previously unreported effects were brain morphological abnormalities, seizures, hearing loss, and heart malformations. These findings broaden the phenotypic spectrum of TAF1/MRXS33 intellectual disability syndrome and the range of TAF1 molecular defects in humans.

Rates of new anal cancer diagnoses and deaths related to human papillomavirus (HPV), the most common sexually transmitted infection, have increased dramatically over the last 15 years, according to researchers at The University of Texas Health Science Center at Houston (UTHealth). The results of their study were published in the November issue of the Journal of the National Cancer Institute.

The study was the first to compare and categorize contemporary national trends in incidence of squamous cell carcinoma of the anus, a type of anal cancer caused by HPV, by stage at diagnosis, year of birth, and mortality. It found that anal cancer diagnoses, particularly advanced stage disease, and anal cancer mortality rates had more than doubled for people in their 50s and 60s. The study also revealed that new diagnoses among black men born after the mid-1980s increased five-fold compared to those born in the mid-1940s.

"Given the historical perception that anal cancer is rare, it is often neglected. Our findings of the dramatic rise in incidence among black millennials and white women, rising rates of distant-stage disease, and increases in anal cancer mortality rates are very concerning," said Ashish A. Deshmukh, PhD, MPH, the study's lead author and an assistant professor at UTHealth School of Public Health.

Anal cancer occurs where the gastrointestinal tract ends and is different from colon or rectal cancer due to the cell type and location where cancer develops. Cancer of the anus is most similar to cervical cancer, a cancer of the tissue that lines a woman's cervix. A distant-stage diagnosis means cancer has spread to other parts of the body, decreasing survival rates. Nearly 90% of anal cancers are caused by HPV.

The researchers analyzed data from all cancer registries in the U.S. and identified 68,809 cases of anal cancer and 12,111 deaths from 2001 to 2016. They found that anal cancer rates and mortality increased by nearly 3% per year - suggesting it may be one of the most rapidly rising causes of cancer incidence and mortality.

The virus is preventable through vaccination, but 50% of Americans are not vaccinated - setting up a potential wave of future infections leading to cancer. The Centers for Disease Control and Prevention recommends a two-dose regimen for children starting the series before age 15 or a three-dose regimen if the series is started at age 16 through 26.

"The vaccine can also be considered for individuals ages 27 to 45 based on shared decision-making, so it is important that adults speak with their health care providers about getting the vaccine," Deshmukh said.

"Screening for anal cancer is not currently performed, except in certain high-risk groups, and the results of this study suggest that evaluation of broader screening efforts should be considered," said senior author Keith Sigel, MD, PhD, MPH, associate professor of medicine at Icahn School of Medicine at Mount Sinai.

Anal cancer is often neglected and stigmatized, despite high-profile deaths such as actress Farrah Fawcett of "Charlie's Angels" fame and the revelation of an anal cancer diagnosis by former "Desperate Housewives" star Marcia Cross, whose husband also developed throat cancer linked to HPV.

"It is concerning that over 75% of U.S. adults do not know that HPV causes this preventable cancer. Educational campaigns are needed to increase awareness about the rising rates of anal cancer and importance of immunization," Deshmukh said.

TORONTO -- Most research on child sexual-abuse survivors focuses on negative consequences such as depression and suicide. A new study instead examines factors associated with resilience and flourishing among adult survivors.

"Remarkably, two-thirds [65%] of the childhood sexual-abuse survivors in our sample met the criteria for complete mental health -- defined as being happy or satisfied with life most days in the past month, having high levels of social and psychological well-being in the past month, and being free of mental illness, suicidal thoughts and substance dependence in the past year," reported lead author Dr. Esme Fuller-Thomson, Professor at the University of Toronto's Factor-Inwentash Faculty of Social Work (FIFSW) and Director of the Institute for Life Course & Aging. "While the prevalence of complete mental health among childhood sexual-abuse survivors is higher than we had expected, it is still substantially less than that found in the general population [77%]. Greater understanding of factors associated with complete mental health among survivors is an important first step in helping survivors achieve the level of well-being found in the general adult population."

The negative association between childhood sexual abuse and complete mental health was completely explained when we took into account the individuals' history of mental illness, substance abuse, chronic pain and social isolation. In other words, we now have an understanding of the pathways that decrease resiliency among child sexual-abuse survivors.

"If the survivors had been depressed at any point in their life, the odds of them currently being in complete mental health declined dramatically. This underlines the importance of mental-health interventions for this population. A promising intervention, cognitive behavioral therapy [CBT], has been tested and found effective at reducing post-traumatic stress disorder and depressive and anxiety symptoms among childhood sexual-abuse survivors," said co-author Dr. Ashley Lacombe-Duncan, a recent doctoral graduate from the FIFSW and Assistant Professor of Social Work at the University of Michigan.

"Having a confidante was found to be the second-strongest single predictor of complete mental health, increasing the odds of past-year complete mental health nearly sevenfold. Given the importance of family and social-support systems, brief interventions to address trauma post-experience and bolster social and familial support are also called for," suggested Dr. Deborah Goodman, Director, Child Welfare Institute, Children's Aid Society of Toronto.

Sexual-abuse survivors who had chronic pain had half the odds of complete mental health compared to those who were free of chronic pain. "It is important that health and social-service professionals help sexual-abuse survivors get the treatment they need to address both their physical health problems, such as chronic pain conditions, in addition to their mental-health concerns," said Dr. Barbara Fallon, Professor at the FIFSW and Canada Research Chair in Child Welfare.

The study, published online ahead of print in Social Psychiatry and Psychiatric Epidemiology, was based on a 2012 Canadian nationally representative survey of 17,014 adults of whom 651 were childhood sexual-abuse survivors. Those who were physically abused during their childhood or who had been exposed to chronic parental domestic violence were excluded from the analysis. "By expanding our research focus from the devastating consequences of childhood sexual abuse to factors correlated with well-being in adulthood, we may be able to help design more effective interventions for those affected to not only survive, but thrive," said Fuller-Thomson.

Using "Trojan horses" to combat cancer from within the tumour cells themselves without damaging healthy tissues is the aim of this new tool created by researchers from the University of Granada (UGR), the Institute of Nanoscience of Aragon (INA), the University of Zaragoza, and the Cancer Research UK Edinburgh Centre at the University of Edinburgh.

The researchers have used exosomes as "Trojan horses" to deliver palladium (Pd) catalysts into cancer cells. "We introduce the catalyst into tiny vesicles or exosomes the size of about 100 nanometres, which are capable of traveling right inside the tumorous cell. Once there, they catalyse a reaction that transforms a passive molecule into a potent anticancer agent," explains Professor Jesús Santamaría of the University of Zaragoza, who, along with Doctor Asier Unciti-Broceta of the University of Edinburgh, has led this study published by the prestigious scientific journal Nature Catalysis.

Participating in the research, entitled "Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis", are Belén Rubio Ruiz of the UGR, María Sancho, Víctor Sebastián, and Manuel Arruebo of the University of Zaragoza, and Pilar Martín-Duque of the Aragonese Foundation for Research & Development (ARAID), an agency created by the Government of Aragon within the INA. The work has been carried out in collaboration with the research group of the University of Edinburgh, led by Dr Asier Unciti-Broceta.

Killing a cancer cell is straightforward: there are many toxic molecules that can perform the task. The challenge is to target the toxic molecule at the cancer cell only, and not at healthy cells. This lack of selectivity in directing anticancer drugs is the cause of the often devastating side effects that cancer patients experience during chemotherapy treatment. Rather than injecting such drugs into the bloodstream, it would be much better if they could be manufactured directly inside the cancer cells. And that is precisely what this international team of scientists has achieved.

"We use catalysts in many aspects of everyday life because they generate chemical reactions that would not otherwise be possible. For example, the gases emitted by our cars pass through a catalyst to make them less harmful to the environment and our health," comments Belén Rubio Ruiz. It is therefore surprising that catalysis, which is known to be so useful in so many fields, is practically unheard-of in oncology. "This is due to the fact that there are tremendous obstacles: identifying suitable catalysts and reactions and, above all, delivering the catalysts directly into the target cells, and not others."

The key: Exosomes

However, exosomes may prove to be the key. Exosomes are secreted by most cells and are surrounded by a membrane containing elements that are characteristic of the cell from which they originate. This renders them selective (thanks to the phenomenon of tropism toward the cells of origin), and makes it possible for them to carry a therapeutic load preferentially to the original cell, even in the presence of other cells.

The authors of the study have found a way to induce the synthesis of catalysts (Pd nanosheets with a thickness of just over one nanometre) inside tumour cell exosomes without disturbing the properties of their membranes--thus converting the exosomes into "Trojan horses" capable of delivering the catalyst to the progenitor cancer cells. Once there, they catalyse the in situ synthesis of an anticancer compound (panobinostat, an anticancer drug approved in 2015).

Having demonstrated the effectiveness of this process in their study, the researchers observe: "We collected exosomes of the same type of cancerous cell that was to be treated, we loaded them with the palladium catalyst and returned them to the culture medium. There, thanks to their selective tropism, the exosomes deliver the catalyst to the original cell. Once inside, the catalyst converts the inactive panobinostat into its active and toxic form, thus killing off the tumour cell just where we want: right inside the tumour cell."

The key to the process is selectivity of the transport mechanism mediated by exosomes. Thanks to this selectivity, panobinostat is only generated within the cells that the catalyst has reached, and hence it preferentially causes the death of the original tumour cells, while the mortality rate among other cells is much lower.

By controlling individual atoms, quantum properties can be investigated and made usable for technological applications. For about ten years, physicists have been working on a technology that can capture and control atoms: so-called nanooptical traps. The technique of capturing microscopic objects with light known from optical tweezers is applied to optical waveguides, in this case a special glass fiber. The glass fiber may only be a few hundred nanometers thin, i.e. about 100 times thinner than a human hair. Laser light of different frequencies is sent into the glass fiber, creating a light field around the waveguide that can hold individual atoms. Up to now, however, the applicability of this technology has been limited by the fact that the atoms have become very hot after a very short time and are lost. The heating rate was three orders of magnitude higher than with optical tweezers, where the light field is generated in free space. Despite an intensive search, it had previously not been possible to determine the cause. Now Daniel Hümmer and Oriol Romero-Isart from the Institute of Quantum Optics and Quantum Information of the Austrian Academy of Sciences and the Department of Theoretical Physics at the University of Innsbruck in cooperation with Philipp Schneeweiss and Arno Rauschenbeutel from the Humboldt University of Berlin have carefully analyzed the system. With their theoretical model, they were able to show that a certain form of mechanical vibration of the glass fiber is responsible for the strong heating of the particles. This is reported by the physicists in the journal Physical Review X.

Mechanical vibrations

"These are the vibrations that arise when you let waves travel along a rope," explains Daniel Hümmer. "The particles, which float only about 200 nanometers above the surface of the waveguide, heat up very quickly because of these vibrations." The heating rate that has now been theoretically determined agrees very well with the experimental results. This finding has important consequences for applications: On the one hand, the technology can be significantly improved with simple counter-measures. Longer coherence times then allow more complex experiments and applications. On the other hand, the physicists suspect that their findings could also be helpful for many similar nanophotonic traps. The theoretical model they have now published provides essential guidelines for the design of such atomic traps. "When manufacturing these traps, not only the optical properties must be taken into account, but also the mechanical properties," stresses Oriol Romero-Isart. "Our calculations here give important indications as to which mechanical effects are most relevant." Since the strength of the interaction between individual atoms and photons is particularly high in nanooptical traps - a problem with which many other concepts struggle - this technology opens the door to a new field of physics. Many theoretical considerations have already been made in recent years. The physicists from Austria and Germany have now cleared away a major obstacle on the way there.

Cold Spring Harbor Laboratory scientists, with chemists and cancer biologists from Dana-Farber Cancer Institute (DFCI), have developed a new therapy that extended the survival of mice with acute myeloid leukemia.

The scientists are the first to demonstrate the anti-cancer effect of blocking the Salt-Inducible Kinase 3 (SIK3) pathway in leukemia using YKL-05-099, a drug developed within the lab of Nathanael Gray at DFCI. SIK3 is a kinase that controls cell division and survival of leukemia cells. Blocking SIK3 prevents leukemia cells from growing.

"Our experiments validate that pharmacological blockade of SIK3 is well-tolerated and extends the survival of leukemic mice," said CSHL Professor Christopher Vakoc, who co-led the study with Kimberley Stegmaier at DFCI. Yusuke Tarumoto, a former postdoctoral researcher in Vakoc's lab, and Shan Lu of Stegmaier's lab are the co-first authors of the paper. Dr. Tarumoto is now a professor at Kyoto University. The team's findings are published in the journal Blood.

Vakoc refers to this type of leukemia treatment as epigenetic therapy, which can change gene activity within the cancer cell. "Because epigenetics is a cellular system that is malleable and dynamic, it's something that we can modulate with drugs," he said. "Developing epigenetic cancer therapies is the core mission of my lab, with SIK3 inhibition in leukemia being our most recently developed strategy."

In 2018, the Vakoc lab used CRISPR genetic screening to identify the SIK3 kinase as a non-obvious leukemia drug target.

"It's an under-studied signaling molecule in the pathogenesis of cancer because it's not mutated in cancer," Vakoc said.

The subtype of leukemia the researchers focused on, MLL, is an aggressive form of cancer that occurs in infants and can be caused by an abnormal rearrangement of chromosomes, which is known as an MLL translocation. "We discovered SIK3 has a very important role in the MLL translocation positive subtype of leukemia," Vakoc said.

The most important finding in this study is in revealing a drug development strategy for treating MLL leukemia.

The new compound created by the team to target SIK3 reprograms a transcription factor, which is a protein that can help turn specific genes on or off by binding to DNA. Vakoc's lab has been at the forefront of trying to reprogram transcription factors in cancer therapy.

"It's widely considered that this is impossible to do," he said. "Our lab wants to challenge that idea."

The study also helped researchers gauge the side effects of the drug. After using YKL-05-099 to suppress SIK3 in mice for a month, the researchers observed the drug to be well-tolerated, not causing any weight loss or significant changes to the animal's normal blood production.

"We took a basic science idea that we published in a paper last year and now we've shown that it may have some usefulness in the clinic," said Vakoc. "This new study advances our fundamental science towards clinical application, and it's a very important milestone in that process."

Hand-dug trenches around Leigh Lake in Grand Teton National Park in Wyoming reveal evidence for a previously unknown surface-faulting earthquake in along the Teton Fault--one occurring about 10,000 years ago.

Together with evidence from the site of a second earthquake that ruptured around 5,900 years ago, the findings published in the Bulletin of the Seismological Society of America extend the history of Teton Fault earthquakes and may offer some clues as to how segments of the fault have ruptured together in the past, the study authors suggest.

The Teton Fault is one of the fastest-moving normal faults in the western United States, separating the eastern edge of the Teton Range from the Jackson Hole basin. The fault is divided into southern, central and northern segments, with the Leigh Lake site falling within the central segment. A previous study identified two Teton Fault earthquakes that occurred 8,000 years ago and 4,700 to 7,900 years ago on the southern segment at Granite Canyon, one of the most famous hiking spots in the Grand Teton National Park.

The younger earthquake at Leigh Lake may be the same rupture as the youngest Granite Canyon earthquake, confirming that there were at least three earthquakes in Holocene times, and that the most recent activity along the fault occurred about 6,000 years ago, said Mark Zellman of BGC Engineering, Inc., the lead author of the BSSA study.

Although the Leigh Lake study doesn't provide a definite answer to the question of whether multiple segments of the Teton fault have ruptured at once, Zellman said the findings "do give us a clue that multi-section ruptures are possible. The overlap in age between the youngest Leigh Lake earthquake and the youngest Granite Canyon earthquake "leaves open the possibility that at least the southern and central section of the Teton fault ruptured together during the most recent event."

Given the Teton fault's high rate of movement in the past, it has been a surprisingly long time since its last earthquake, said Zellman. "The seemingly regular and relatively short intervals of time between these three events makes the long period of quiescence on the Teton fault even more surprising," he said. "I was expecting that we would have found evidence for at least one rupture that post-dates the youngest event known from Granite Canyon."

Zellman and colleagues chose Leigh Lake as a study site because no other paleoseismic studies had been conducted previously on this central segment of the fault, and because the site offered several small and easy to reach scarps for shovel excavations. The researchers excavated at two of three scarps that represent the fault's movement in postglacial times.

The remoteness of the site and its location within a national park prevented the researchers from using heavy equipment to dig and backfill their shallow trenches. In the future, Zellman said, "it would be nice to identify a location or two where we could excavate a deeper trench to expose a longer record."

Asked about the older event at Granite Canyon that was not found at Leigh Lake, Zellman said "evidence for that earthquake might be preserved in the third scarp. But we won't know for sure until we excavate that scarp."

The researchers examined the coarse exposed sediments in the trenches for signs of past faulting, in some places analyzing the orientation of large rocks clasts within the trench walls to reveal the fault's presence. The faults were dated using radiocarbon and optically stimulated luminescence methods.

Based on the length of the fault ruptures, Zellman and colleagues estimate the 10,000-year old earthquake may have been a magnitude 6.6 to 7.2 quake, while the 5,900-year old earthquake may have been magnitude 7.0 to 7.2.

Zellman said other studies of sites along the fault's northern segment, combined with data from studies that look at landslides and other signs of paleoseismic activity contained in deep lake sediments from the region, will help further fill in the history of the Teton Fault.