Culture

Students attending a high school in Germany can decide whether to begin the schoolday at the normal early time or an hour later. According to Ludwig-Maximilians-Universitaet (LMU) in Munich chronobiologists, the measure has had a positive effect on both their sleep and learning experience.

They fall asleep too late at night, and are rudely expelled from dreamland by the shrill tones of the alarm clock in the morning. Classes begin early and they must be prepared to show their mettle.

Adolescents are constantly sleep deprived, a phenomenon that can be observed worldwide. In addition, the problem is no longer confined to certain personality types and therefore of individual concern, it has become a public health issue. Indeed, the Centers for Disease Control and Prevention in the US have officially designated the matter as a public health concern. The consequences of chronic sleep deficit include not only a reduced ability to concentrate but also an increased accident risk to and from school. Studies have also detected higher risks for depression, obesity, diabetes and other chronic metabolic diseases. In light of these findings, it is hardly surprising that calls for school classes to begin later in the morning are becoming louder.

But would such a move do any good? Would a later school start actually change the sleep of adolescents for the better, and enhance their cognitive performance in class? So far, there have been few research studies of this question in Europe. A group of chronobiologists in Munich, led by Eva Winnebeck and Till Roenneberg, studied the issue at a high school in Germany that made an exceptional change to their starting time arrangement. This school instituted a system that allows senior students to decide day by day whether or not to attend the first class of the day or to come to school an hour later. This form of flexible scheduling is possible because the school has adopted what is known as the Dalton Plan (for which the institution won the German School Prize in 2013). A major component of this idea (which originated in the US) is that students are required to tackle parts of the school curriculum independently in the context of project phases. The school timetable allots 10 hours per week for these activities, half of which are scheduled for the first class at 8 o'clock in the morning. Students who choose to skip this class must work through the material in their free periods during the day or after the end of the regular school day. Students from the three senior grades (i.e. 15- to 19-year-olds) served as the study population for LMU researchers from the Institute of Medical Psychology. For 3 weeks before and 6 weeks after the introduction of the flexible system in the school in Alsdorf, the team observed how the students reacted and adapted to the change. The participating students were asked to record their sleeping patterns daily, and around half of them were equipped with activity monitors for objective sleep monitoring. At the end of the study, the participants provided information on their sleep, their overall level of satisfaction and their ability to concentrate in class and while studying course content.

The team was initially surprised by the fact that the students made relatively little use of the new-found freedom to start school later, says Eva Winnebeck. On average, they chose to miss out on the first class twice a week. On these days, they slept more than an hour longer than usual, irrespective of gender, grade, chronotype or frequency of later school starts. In other words, nearly all of the students involved in the project benefited when going later. In contrast to the era of rigid school start times, however, the switch to flexible starts did not result in a significant increase in the overall duration of students' sleep. Nevertheless, the students were very satisfied with the new scheduling model. The vast majority of students reported that they slept better and were better able to focus on the course material in school. "Perhaps the very fact that one can decide for oneself when to get up in the morning is sufficient to break the cycle and reduce the pressure," says Winnebeck. According to the authors of the study, which appears in the journal Sleep, "flexible systems are a viable alternative for implementing later school starts to improve teenage sleep." But they also underline the importance of actively encouraging students to make use of the option to start the school day later.

For years, physicians have been aware that patients carrying the apolipoprotein E4 (APOEε4) gene are at a greater risk of developing Alzheimer's disease. New research from McGill University has now found the gene plays an even greater role in dementia.

In a study published today in the Journal of the American Medical Association: Neurology, Dr. Pedro Rosa-Neto's research team from the Douglas Mental Health University Institute's Translational Neuroimaging Laboratory found that the risk of developing dementia conferred by APOEε4 does in fact involve processes associated to tau aggregation.

A tale of two proteins

Of all the genetics risk factors for sporadic Alzheimer's disease, APOEε4 is the single most important.

"Alzheimer's disease is defined by the aggregation of two proteins in the brain: amyloid plaques and tau tangles, both of which are known to be neurotoxic" explains Joseph Therriault, a PhD student in the McGill's Integrated Program in Neuroscience under the supervision of Drs. Pedro Rosa-Neto and Serge Gauthier. "APOEε4 has been associated with amyloid plaques, but its association with tau tangles has been controversial. In our study of nearly 500 individuals, we demonstrate this association in living humans."

Therriault and his colleagues assessed two independent populations thanks to data available through the Translational Biomarkers in Aging and Dementia (TRIAD) cohort and the Alzheimer's Disease Neuroimaging Initiative (ADNI), two research initiatives in which participating patients agreed to complete a variety of imaging and clinical assessments. In both instances, MRIs and PET scans were used to establish a relationship between APOEε4 and tau tangles.

Tau tangles and memory

"For years, we have known that people with the APOEε4 gene have more memory problems," adds Therriault, who is also the study's lead author. "We were able to show that carriers of this gene also had greater levels of tau tangles in memory centers of the brain, even after controlling for how much amyloid plaques they had."

While this study does not identify a biological mechanism for why this association exists, the findings contribute to an evolving framework in which APOEε4 plays a central role in Alzheimer's disease because of its role in both amyloid plaques and tau tangles.

Dr. Rosa-Neto adds that APOEε4 has an important role in the very early stages of Alzheimer's disease. "This paper highlights why APOEε4 carriers show early memory deficits that eventually lead to dementia," he says.

"Our paper is an important step forward because we provide evidence that the substantial increased risk of developing dementia conferred by APOEε4 genotype is related to both of the hallmark pathologies of Alzheimer's disease," concludes Therriault.

The team next hopes to determine whether the studied individuals accumulate tau at a faster level through longitudinal imaging to see how subjects evolve over time.

Therriault, Rosa-Neto and Gauthier are hopeful that the research will help clinicians better assess the early signs of Alzheimer's disease.

HUNTINGTON, W.Va. - Findings from a recent research project, conducted by a Marshall University scientist and assistant professor in the Marshall University College of Science, with researchers in Texas, was recently published in the December issue of the prestigious online journal, Nature Communications.

Dr. Eugene Shakirov is studying the connection between ribosomes and telomeres in plants. Telomeres are the physical ends of chromosomes and they shorten with age in most cells. Accelerated shortening of telomeres is linked to age-related diseases and overly long telomeres are often linked to cancer.

Telomere length varies between individuals at birth and is known to predetermine cellular lifespan, but the genes establishing telomere length variations are largely unknown. The research being done by Shakirov, along with collaborators at the University of Texas at Austin, Texas A&M University, HudsonAlpha Institute for Biology and the Kazan Federal University in Russia focused on the study of the genetic and epigenetic causes of natural telomere length variation in Arabidopsis thaliana, a small flowering plant

To find those genes that establish telomere length variations, Shakirov used the plant to look further into which genes cause the variations of the telomeres. Using genomic and genetic tests, the research team identified three genes in plants, NOP2A, RPL5A and RPL5B, as being important for telomere length control. Those same genes also play important roles in cellular processes and ribosome biogenesis and show that the identified genes perform multiple tasks in plant cells and tie together two seemingly different, but equally important, processes: the telomere length control and ribosome biology.

Shakirov says the new findings show a clear genetic link between components of ribosome biogenesis pathway and telomere length, mapping a new direction for understanding and potentially treating human diseases caused by mutations in genes that control both the ribosome and telomere.

"We need to fully understand the role of plant and human NOP2 and RPL5 genes in telomere length control and ribosome biology, so in the future we'll run detailed molecular analysis on these genes." Shakirov said. "Some of the lessons we learn from plant telomere proteins may provide new avenues for identification and treatment for human diseases."

Chestnut Hill, Mass. - Purchasing luxury goods can affirm buyers' sense of status and enjoyment of items like fancy cars or fine jewelry. However, for many consumers, luxury purchases can fail to ring true, sparking feelings of inauthenticity that fuel what researchers have labeled the "impostor syndrome" among luxury consumers.

"Luxury can be a double-edged sword," write Boston College Carroll School of Management Associate Professor of Marketing Nailya Ordabayeva and her co-authors, Harvard Business School doctoral student Dafna Goor, Boston University professor Anat Keinan, and Hult International Business School professor Sandrine Crener. "While luxury consumption holds the promise of elevated status, it can backfire and make consumers feel inauthentic, producing what we call the 'impostor syndrome from luxury consumption.'"

That's how Ordabayeva and co-authors explain the crux of the projects' findings, published in the Journal of Consumer Research. The team draw their conclusions based on nine studies, encompassing surveys and observations of patrons of the Metropolitan Opera and shoppers at Louis Vuitton in New York City, vacationers on Martha's Vineyard, and other luxury consumers.

In contrast to previous studies in this area, "we find that many consumers perceive luxury products as a privilege which is undue and undeserved," according to Ordabayeva and her co-authors.

As a result, consumers feel inauthentic while wearing or using these products, and they actually act less confident than if they were sporting non-luxury items. For example, "one participant said she felt very shy when she wore a gold necklace with diamonds that she owned because it is not in her character to wear luxurious jewelry," even though she could afford it.

This effect is mitigated among consumers who have an inherently high sense of entitlement, and also among non-entitled-feeling consumers on occasions that make them feel special, such as their birthday.

"Luxury marketers and shoppers need to be aware of this psychological cost of luxury, as impostor feelings resulting from purchases reduce consumer enjoyment and happiness," said Ordabayeva. "But boosting consumers' feelings of deservingness through sales tactics and marketing messages can help. Ultimately, in today's age that prioritizes authenticity and authentic living, creating experiences and narratives that boost people's personal connection with products and possessions can yield lasting benefits for consumers and marketers alike."

REM - Rapid Eye Movement - is not only the name of a successful American rock band, but also and not least a characteristic eye movement in paradoxical sleep, so in the stage with high dream activity. This sleep phase has a peculiarity: Although the muscle tone of the sleeping person completely relaxed, the eyes suddenly move back and forth. The name "paradoxical sleep" is well deserved. Characteristic of these are signs of deep sleep (muscle atony) in connection with a brain activity, which is very similar to those in the waking state, and eye movements. This sleep phase was discovered in the 1950s by French and American researchers and consequently called rapid eye movement sleep (REM sleep), i.e. sleep with rapid eye movements. Why can this strange phenomenon be useful? For 70 years, scientists have been dreaming of getting to the bottom of the mystery. Thanks to the productive cooperation between the universities of Bern and Fribourg, this dream could now come true.

Butterfly wings arranged neurons

For several years, the team led by Franck Girard and Marco Celio at the University of Freiburg has studied neurons under the microscope, which occur in the brain stem and form a structure that is reminiscent of butterfly wings, which is why she was baptized Nucleus papilio. "These neurons are associated with multiple nerve centers, especially those responsible for eye movement, and those involved in sleep control," explains Franck Girard. "Therefore, we asked ourselves the following question: may the nucleus papilio neurons play a role in the control of eye movements during sleep?"

Stronger together

To test this hypothesis, the Freiburg researchers turned to the research group headed by Dr. C. Gutiérrez Herrera and Prof. A. Adamantidis at the Department of Neurology at the Inselspital, University Hospital Bern, and Department for BioMedical Research of the University of Bern, who are investigating sleep in mice. "To our surprise, we found that these neurons are particularly active in the phase of paradoxical sleep," reports Dr. Carolina Gutierrez. The researchers from Bern gathered the loop around the nucleus papilio neurons even more closely and were able to demonstrate with the help of optogenetic methods (combined optical and genetic techniques) that their artificial activation causes rapid eye movement, especially during this sleep phase. Conversely, the inhibition or elimination of these same neurons blocks the movement of the eyes.

After the "how" the "why"!

Now that it is clear that the nucleus papilio neurons play an important role in eye movement during REM sleep, it is important to find out what function this phenomenon has. Is it due to the visual experience of dreams? Does it matter in preserving memories? "Now that we are able to specifically activate the nucleus papilio 'on demand' in mice by optogenetic methods, we may be able to find answers to these questions," says Antoine Adamantidis. The next step, however, will be to confirm the activation of nucleus papilio neurons during REM sleep in humans. The researchers have not yet found the key to their dreams, but they've come a long way.

A better understanding of the neural circuits involved in paradoxical sleep is therefore a prerequisite for understanding for instance how these neurons are prone to degenerative changes in diseases such as Parkinson's.

East Hanover, NJ. December 20, 2019. Kessler Foundation researchers reported results of a study of deficits in prospective memory in individuals with multiple sclerosis (MS) that may contribute to difficulties with everyday life activities. The article, "Time-based prospective memory is associated with functional performance in persons with MS," (doi: 10.1017/S135561771900095X) was epublished on September 23, 2019 by the Journal of the International Neuropsychological Society.

The authors are Erica Weber, PhD, Nancy Chiaravalloti, PhD, and John DeLuca, PhD, of Kessler Foundation, and Yael Goverover, PhD, of New York University, who is a visiting scientist at Kessler Foundation. Drs. Weber and Goverover are former recipients of Switzer Fellowships awarded to postdoctoral fellows by the National Institute on Disability Independent Living and Rehabilitation.

Link to abstract: DOI: https://doi.org/10.1017/S135561771900095X

While interest in memory difficulties in the MS population has grown, most studies focus on retrospective memory, or the recall of previously learned information. Few studies have addressed difficulties with prospective memory, which are associated in general with poor everyday like functioning, and in MS specifically, with greater likelihood of unemployment. Prospective memory entails remembering to perform an intention at a future point in time, or "remembering to remember".

In this study, participants were presented with two types of prospective memory tasks - event-based tasks, which have relatively low strategic cognitive demands, and time-based tasks, which require more higher-order resources for successful completion. One example of an event-based task would be remembering to mail a letter when passing a post office; an example of a time-based task would be remembering to call the doctor on Wednesday morning. This is only the second study to directly compare time- and event-based prospective memory in MS.

Researchers compared 30 adults with MS (aged 28-65) with 30 healthy controls. All participants underwent neuropsychological assessment, prospective memory assessment (Memory for Intentions Screening Test, MIST), and an everyday functioning assessment developed at Kessler Foundation (KF-Actual Reality TM ), which presents individuals with three online purchasing tasks.

Results showed that compared to the control group, the MS group had more difficulty with tests of prospective memory, and their performance was poorer on time-based tasks than on event-based tasks. There was correlation between performance on the KF-Actual Reality and the time-based, but not the event-based tasks on the MIST. Time-based deficits were associated with deficits in executive function, as well as lower motor scores, indicating a possible link between prospective memory and MS disease severity, according to Dr. Weber, research scientist in the Center for Traumatic Brain Injury Research.

"Poor prospective memory hinders the ability to perform a broad range of everyday life activities, which undermines individuals' independence," noted Dr. Weber. "Our findings indicate that developing strategies that improve time-based functioning may help individuals with MS improve their prospective memory and support their efforts to maintain their independence."

HOUSTON - (Dec. 20, 2019) - The solar wind that pummels the Earth's dayside magnetosphere causes turbulence, like air over a wing. Physicists at Rice University have developed new methods to characterize how that influences space weather on the nightside.

It's rarely quiet up there. The solar wind streams around the Earth and cruises off into the night, but closer to the planet, parcels of plasma get caught in the turbulence and sink back toward Earth. That turbulence causes big ripples in the plasma.

With the help of several spacecraft and computational tools developed over the past decade, Rice scientists led by space plasma physicist Frank Toffoletto can now assess the ripples, called buoyancy waves, caused by the turbulence.

These waves, or oscillations, have been observed in the thin layer of magnetic flux along the base of the plasma sheet that tails away from the planet's nightside. The Rice theory is the first to quantify their motion.

The theory adds another element to the Rice Convection Model, an established, decades-in-the-making algorithm that helps scientists calculate how the inner and middle magnetosphere will react to events like solar storms that threaten satellites, communications and power grids on Earth.

The new paper in JGR Space Physics by Toffoletto, emeritus professor Richard Wolf and former graduate student Aaron Schutza starts by describing the bubbles -- "bursty bulk flows" predicted by Wolf and Rice alumnus Duane Pontius in 1990 -- that fall back toward Earth through the plasma tail.

Functionally, they're the reverse of buoyant air bubbles that bob up and down in the atmosphere because of gravity, but the plasma bubbles respond to magnetic fields instead. The plasma bubbles lose most of their momentum by the time they touch down at the theoretical, filamentlike boundary between the inner plasma sheet and the protective plasmasphere.

That sets the braking boundary into a gentle oscillation, which lasts mere minutes before stabilizing again. Toffoletto compared the motion to a plucked guitar string that quickly returns to equilibrium.

"The fancy name for this is the eigenmode," he said. "We're trying to figure out the low-frequency eigenmodes of the magnetosphere. They haven't been studied very much, though they appear to be associated with dynamic disruptions to the magnetosphere."

Toffoletto said the Rice team has in recent years discovered through simulations that the magnetosphere doesn't always respond in a linear fashion to the steady driving force of the solar wind.

"You get all kinds of wave modes in the system," he said, explaining that bursty bulk flows are one such mode. "Every time one of these things come flying in, when they hit the inner region, they basically reach their equilibrium point and oscillate with a certain frequency. Finding that frequency is what this paper is all about."

As measured by the THEMIS spacecraft, the periods of these waves are a few minutes and the amplitudes are often bigger than the Earth.

"Understanding the natural frequency of the system and how it behaves can tell us a lot about the physical properties of plasma on the nightside, its transport and how it might be related to the aurora," he said. "A lot of these phenomena show up in the ionosphere as auroral structures, and we don't understand where these structures come from."

Toffoletto said the models suggest buoyant waves may play a role in the formation of the ring current that consists of charged particles that flow around Earth as well as magnetospheric substorms, all of which are connected to the aurora.

He said that no more than a decade ago, many magnetosphere simulations "would look very uniform, kind of boring." The Rice group is collaborating with the Applied Physics Laboratory to include the Rice Convection Model in a newly developed global magnetosphere code called "Gamera," named after the fictional Japanese monster.

"Now, with such higher-resolution models and much better numerical methods, these structures are starting to show up in the simulations," Toffoletto said. "This paper is one little piece of the puzzle we're putting together of how the system behaves. All this plays a big role in understanding how space weather works and how that in turn impacts technology, satellites and ground-based systems."

The Rice Convection Model itself was refreshed this month in a paper led by recent Rice alumnus Jian Yang, now an associate professor of Earth and space sciences at the Southern University of Science and Technology, Shenzhen, China.

Tiny solutions are being sought for big liver problems by a scientist at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth).

Armed with two grants totaling $3.6 million from the National Institutes of Health (NIH), Cynthia Ju, PhD, professor, vice chair for research of anesthesiology and co-director of the Center for Perioperative Medicine at McGovern Medical School, is studying molecules linked to life-threatening liver injuries.

The idea is to identify molecules that play a major role in the injury process and then develop ways to either enhance their activity or block them. These molecules are sometimes called drug targets or biologics.

One grant is to mitigate the liver injury that occurs during a transplant, and the other is to lessen the damage that happens during an acetaminophen overdose.

In the liver transplantation study, Ju and her collaborator Wasim Dar, MD, PhD, associate professor of surgery at McGovern Medical School, will build on earlier work showing that a white blood cell known as an eosinophil protects the liver during transplantation.

Ju's grant is to further study the role of IL-33/ST2 signaling in eosinophils and how that signaling leads to protection in order to find potential avenues for therapeutic intervention.

The liver is the second most commonly transplanted major organ, after the kidney, reports the United Network of Organ Sharing. In 2017, 8,082 patients received a liver transplant and 13,885 patients in the United States were on the waiting list for a liver transplant.

In the acetaminophen study, Ju and Zhiqiang An, PhD, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School, are trying to address the alarming number of liver failure cases linked to acetaminophen overuse. It is responsible for nearly half of liver failure cases in intensive care units across the country.

"Patients with Tylenol overdose-induced liver failure also have thrombocytopenia, a significant platelet reduction in the blood," Ju said. "Where the platelets went had been a mystery."

Ju studied liver biopsies from liver failure patients due to the overdose of acetaminophen and found an abundance of platelets in the liver. Interestingly, she found that depletion of platelets in the liver markedly reduced acetaminophen-induced liver injury in mice, suggesting that the excess platelets are causing liver damage. The grant will allow Ju to further study Chi3l1 signaling and the underlying mechanism accounting for its role in causing acute liver injury.

Patients who were transplanted with hearts from hepatitis C-positive donors had comparable outcomes after one year to patients who received hearts from donors that didn't have the disease, according to a Vanderbilt University Medical Center study published in JAMA Cardiology.

Using such hearts, which would have been largely discarded a few years ago before direct-acting antiviral therapies were proven effective, presents an opportunity to expand the donor pool, shorten wait times for organs and ensure that fewer people die waiting for them.

The prospective, single-center observational study looked at 80 adult patients at Vanderbilt University Medical Center who received a heart transplant from hepatitis C-positive donors between September 2016 and May 2019.

The Vanderbilt Transplant Center is believed to be the largest user of hepatitis C-positive donor organs in the world, the study notes. VUMC has greatly expanded the use of such hearts to patients since 2016 because of the proven efficacy of direct-acting antiviral therapies, which can cure hepatitis C infection in patients after 12 weeks of treatment.

Side effects from the therapies are minimal, said Kelly Schlendorf, MD, MHS, lead author of the study and medical director of VUMC's Adult Heart Transplant Program.

"For several decades, the number of heart transplants performed annually in the United States has been relatively stagnant," Schlendorf said.

"Over the past few years, however, heart transplant volumes are on the rise, due in part to transplantation using hepatitis C-positive donors. These donors offer a strategy to safely expand the donor pool and allow more patients to undergo transplant. When you consider the alternative, that's a big deal."

Between 2016 and 2018, 37% of Vanderbilt's heart transplants were from hepatitis C-positive donors, a factor in allowing Vanderbilt to double the number of heart transplants, from 130 between 2013 and 2015 to 260 between 2016 and 2018. Vanderbilt is now the second-largest heart transplant program by volume in the country.

As more organs become available, time on waitlists decreases. In the cohort of patients described in Vanderbilt's study, mean wait time once patients agreed to receive a hepatitis C-positive heart was only four days, compared with national reported median wait times between 70 and 535 days.

Less time on the waiting list means less need for prolonged mechanical circulatory support, and lower risk of complications like kidney failure, infection, stroke or death, Schlendorf said. The risk of dying on the waiting list is at least 10% and increases the longer the patient has to wait.

"Without a doubt, the use of hepatitis C-positive hearts has allowed some of our patients who would not have otherwise achieved heart transplant to do so, and for many of them, to do so quickly," she said.

Hepatitis C-positive donor hearts have become more commonplace, particularly in this region of the country, because of increased drug overdose deaths due to the opioid crisis. "This is probably the only silver lining to an otherwise tragic epidemic," Schlendorf said, noting that transplant centers located in regions where the opioid crisis is less prevalent may not benefit as much from these hearts as Vanderbilt has.

Schlendorf also noted that further work is needed to clarify longer term outcomes in these patients.

"There is a growing consensus among the transplant community as a whole that organs from hepatitis C-positive donors should not be wasted," she said. "We were among the first centers to start using these donors for heart transplantation but since then many other centers have followed suit."

An astonishing number of recent technological advances and novel engineering applications go hand in hand with progress in the field of materials science. The design and manipulation of materials at the nanoscale (that is, on the order of billionths of a meter) has become a hot topic. In particular, nanosheets, which are ultra-thin 2D planar structures with a surface ranging from several micrometers to millimeters, have recently attracted much attention because of their outstanding mechanical, electrical, and optical properties. For example, organic nanosheets have great potential as biomedical or biotechnological tools, while inorganic nanosheets could be useful for energy storage and harvesting.

But what if we could go from a 2D nanosheet structure to a molecular 3D structure in a controllable and reversible way? Scientists from the Tokyo Tech and The University of Tokyo have conducted a study on such a reversible 2D-3D conversion process, motivated by its potential applications. In their study, published in Advanced Materials, they first focused on converting spherical lipid vesicles (bubble-like structures) into 2D nanosheets through the cooperative action of two compounds: a membrane-disruptive acidic peptide called E5 and a cationic copolymer called poly(allylamine)-graft-dextran (or PAA-g-Dex, for short). They then attempted to revert the lipid nanosheets back to their 3D vesicle form by modifying specific conditions, such as pH, or using an enzyme (Fig. 1), and found that the reaction was reversible.

Thus, through various experiments, the scientists elucidated the mechanisms and molecular interactions that make this reversible conversion possible. In aqueous media, planar lipid bilayers tend to be unstable because some of their hydrophobic (water-repelling) tails are exposed on the edges, leading to the formation of vesicles, which are much more stable (Fig. 2). However, peptide E5, when folded into a helical structure with the aid of PAA-g-Dex, can disrupt the membrane of these vesicles to form 2D nanosheets. This pair of compounds combine into a belt-like structure on the edges of the nanosheets, in a process that is key to stabilizing them. Professor Atsushi Maruyama, who led this research, explains "In the sheet structures observed in the presence of E5 and PAA-g-Dex, the assembly of E5 and the copolymer at the sheet edges likely prevents the exposure of the hydrophobic edges to the water phase, thus stabilizing the nanosheets." (see Fig. 3) The sheets can be converted back to spherical vesicles by disrupting the belt-like structure. This can be done by, for example, adding the sodium salt of poly(vinylsulfonic acid), which alters the helical shape of E5.

The scientists' experiments showed them that the nanosheet is very stable, flexible, and thin; these are properties that are valuable in biomembrane studies and applications. For instance, the 2D-3D conversion process can be used to encapsulate molecules, such as drugs, in the vesicles by converting them into sheets and then back into spheres. "Lipid vesicles are used for both basic studies and practical applications in pharmaceutical, foods, and cosmetic sciences. The ability to control the formation of nanosheets and vesicles will be useful in these fields," concludes Prof. Maruyama. Undoubtedly, improving our ability to manipulate the nanoscopic world will bring about positive macroscopic changes to our lives.

Existing genetic variation in natural populations of Mediterranean mussels allows them to adapt to declining pH levels in seawater caused by carbon emissions. A new study by biologists from the University of Chicago shows that mussels raised in a low pH experimental environment grew smaller shells than those grown at normal pH levels, but the overall survival rate of mussels grown under both conditions was the same.

The surviving population in the low pH environment differed genetically from the others, suggesting that genetic variants that already exist in a subset of the natural population of mussels allowed them to adapt to the harsher new environment. This could be good news for conservationists and seafood lovers alike, as the culinary delicacy finds ways to adjust to the changing seas.

"The hope is there are already a few individuals in the species that already have some genetic makeup that allows them to withstand the change in the environment," said Mark Bitter, a graduate student at UChicago who led the study, published December 20, 2019, in Nature Communications. "This effectively allows evolution to work a lot faster if you're not waiting around for some new mutation to arise."

As humans continue to burn more and more fossil fuels, the oceans absorb roughly one third of the extra carbon released into the atmosphere. This in turn causes pH levels of seawater to drop, making it more acidic. Mussels, oysters and certain species of algae have difficulty producing their hard, calcium carbonate shells in this environment. In a 2016 study, Cathy Pfister, PhD, the senior author of the new study and co-director of the Microbiome Center at UChicago, showed that modern mussel shells collected in the Pacific Northwest were on average 32 percent thinner than those from the 1970s.

Bitter and his teammates worked at the Laboratoire d'Oceanographie in Villefranche-sur-Mer, on the Mediterranean coast of France. The project was sponsored by the France and Chicago Collaborating in the Sciences (FACCTS) program, designed to encourage collaboration among UChicago scientists and research teams at institutions of higher learning in France.

Over the course of three research trips to France in 2016 and 2017, researchers collected specimens of Mytilus galloprovincialis, the Mediterranean mussel, one of several mussel species that provides a valuable food source worldwide. They carefully bred dozens of combinations from 12 females and 16 males to ensure a genetically diverse population of larvae -- 192 different combinations total.

With that starting population, they divided the larvae into two groups: one to develop in water with the normal, ambient pH level of 8.1, and the other in seawater with a pH of 7.4. This value is actually lower than what these mussels currently experience in the wild. The global average pH of the oceans is about 8.0; Mediterranean mussels can encounter values down to 7.7 in some locations. The lower 7.4 pH used in the experiment falls below projected global mean declines in seawater pH over the next 100 years, but may be encountered by marine species inhabiting coastal habitats before the end of the century.

The mussel larvae, over 1 million individuals in total, were kept in a series of buckets, with carbon dioxide-manipulated seawater pumped in from head tanks to carefully regulate the pH levels in the larval cultures. The buckets were equipped with motorized paddles to circulate the water naturally. As the larvae grew and developed shells, they ultimately latched on to the vertical sides of the buckets.

Over the span about six weeks, Bitter and his teammates took samples every few days to measure shell size and analyze the genetic makeup of the surviving larvae. In general, the mussels in the ambient pH conditions grew their shells at a faster rate than the ones in lower pH water, although after two weeks the low pH population mostly caught up. Bitter suspects this may be because the individuals most vulnerable to low pH conditions died before this point, and the survivors were able to continue growing normally.

When the researchers analyzed the genetic variation in the two test groups, they saw strong signatures of selection in the low pH conditions, meaning that a unique genetic background emerged among the mussels able to withstand that environment. After day six, they separated the fastest shell growers from the slowest in each pH environment. Shell size is an indicator of fitness -- the mussels with the largest shells were likely the strongest competitors. But if one mussel grows its shell the fastest in current ocean conditions, does that mean it's also going to do well in a more extreme, low pH scenario?

"The answer is no," Bitter said. "There seems to be a very unique kind of genetic makeup of the individuals that end up growing best in the low pH environment, relative to the ambient conditions."

At the end of the experiment, there was no difference in the total survival of mussels raised in either environment. This would seem like rare good news in the context of rapidly advancing climate change: a species that already has the ability to adapt to harsher conditions. But Bitter points out that pH is just one variable expected to change in the near future.

"Some of these individuals are really good at dealing with this huge reduction in pH. But what if you also reduce salinity or change the temperature substantially?" he said. "Just because you can run a marathon doesn't mean you can turn around and swim right after that. It's a multi-stressor scenario."

He says this study shows why it's important to focus conservation and aquaculture efforts on maintaining broad genetic diversity among mussel populations, since the ability to adapt to near future conditions appears to exist already in the gene pool.

"We have already seen substantial declines in shell size of one mussel species in nature, but it does look like there is this capacity for this species to adapt," he said, "which is some good news amidst a lot of bleakness."

A comprehensive map of genes necessary for cancer survival is one step closer, following the validation of the two largest CRISPR-Cas9 genetic screens in 725 cancer models, across 25 different cancer types. Scientists at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard compared the consistency of the two datasets, independently verifying the methodology and findings.

The results, published today (20 December 2019) in Nature Communications, mean that the two datasets can be integrated to form the largest genetic screen of cancer cell lines to date, which will provide the basis for the Cancer Dependency Map in around 1,000 cancer models. The scale of this combined dataset will help to speed up the discovery and development of new cancer drugs.

The Cancer Dependency Map (Cancer DepMap) initiative* aims to create a detailed rulebook of precision cancer treatments for patients. Two key elements of the Cancer DepMap are the mapping of the genes critical for the survival of cancer cells and analytics of the resulting datasets. Despite recent advances in cancer research, making precision medicine widely available to cancer patients requires many new drug targets.

To find these drug targets, Cancer DepMap researchers take tumour cells from patients to create cell lines that can be grown in the laboratory. They then use CRISPR-Cas9 technology to edit the genes in these cancer cells, turning them off one-by-one to measure how critical they are for the cancer to survive. The results of these experiments indicate which genes are the most likely to make viable drug targets.

In this new study, researchers analysed data from two recently published CRISPR-Cas9 genetic screens performed on cancer cell lines at the Broad and Sanger Institutes. Despite significant differences in experimental protocols, the team found that the screen results were consistent with one another. Crucially, the same genes essential to cancer survival - known as dependencies - were found in both datasets.

Dr Clare Pacini, a first author of the study from the Wellcome Sanger Institute and Open Targets, said: "The Sanger and Broad Institute CRISPR-Cas9 screens were created using slightly different protocols, such as cell growth duration and reagents used. To verify each Institute's dataset, we have repeated CRISPR-Cas9 screens using the protocols originally employed at the other Institute. Importantly, we have found the same genetic dependencies in each, meaning the new drug targets originally identified are consistent."

Aviad Tsherniak, of the Broad Institute of MIT and Harvard, said: "This is the first analysis of its kind and is really important for the whole cancer research community. Not only have we reproduced common and specific dependencies across the two datasets, but we have taken biomarkers of gene dependency found in one dataset and recovered them in the other. Our analysis has been unbiased, rigorous and proves the veracity of the approach and the drug targets identified."

In 2013, results comparing two large pharmacogenomic datasets employing the cancer models used in this study raised concerns about the reproducibility of the experiments performed. Further independently-published analyses eventually proved the two resources to be reliable and consistent, restoring confidence in the robustness of large-scale drug screens, but the episode slowed the progress of cancer research.

This study validates the reproducibility of CRISPR-Cas9 functional genetic screens in order to remove any doubt about their efficacy. It sets rigorous standards for assessing these new types of dataset, facilitating the comparison and integration of large databases of cancer dependencies.

Dr Francesco Iorio, of the Wellcome Sanger Institute and Open Targets, said: "It is worth remembering that when these datasets were originally produced we were dealing with a new, unproven technology. This study is important because it demonstrates the validity of the experimental methods and the consistency of the data that they produce. It also means that two large cancer dependency datasets are compatible. By joining them together, we will have access to much greater statistical power to narrow down the list of targets for the next generation of cancer treatments."

WEST LAFAYETTE, Ind. - One of the challenges in using machine learning for drug development is to create a process for the computer to extract needed information from a pool of data points. Drug scientists must pull biological data and train the software to understand how a typical human body will interact with the combinations that come together to form a medication.

Purdue University drug discovery researchers have created a new framework for mining data for training machine learning models. The framework, called Lemon, helps drug researchers better mine the Protein Data Base (PDB) - a comprehensive resource with more than 140,000 biomolecular structures and with new ones being released every week. The work is published in the Oct. 15 edition of Bioinformatics.

"PDB is an essential tool for the drug discovery community," said Gaurav Chopra, an assistant professor of analytical and physical chemistry in Purdue's College of Science who works with other researchers in the Purdue Institute for Drug Discovery and led the team that created Lemon. "The problem is that it can take an enormous amount of time to sort through all the accumulated data. Machine learning can help, but you still need a strong framework from which the computer can quickly analyze data to help in the creation of safe and effective drugs."

The Lemon software platform is a fast C++11 library with Python bindings that mines the PDB within minutes. Loading all traditional mmCIF files in the PDB takes about 290 minutes, but Lemon does this in about six minutes when applying a simple workflow on an 8-core machine. Lemon allows the user to write custom functions, include it as part of their software suite, and develop custom functions in a standard manner to generate unique benchmarking datasets for the entire scientific community.

"Experimental structures deposited in PDB have resulted in several advances for structural and computational biology scientific and education communities that help advance drug development and other areas," said Jonathan Fine, a PhD student in chemistry who worked with Chopra to develop the platform. "We created Lemon as a one-stop-shop to quickly mine the entire data bank and pull out the useful biological information that is key for developing drugs."

Lemon got its name as it was originally designed to create benchmarking sets for drug design software and identify the lemons, biomolecular interactions that cannot be modeled well, in the PDB.

The software development work is the latest project involving health innovations from Chopra and his team. Lemon is freely available on GitHub at https://github.com/chopralab/lemon. Detailed documentation is available at https://chopralab.github.io/lemon/latest/index.html.

Chopra also worked with the Purdue Research Foundation Office of Technology Commercialization to patent other innovations from his lab. For more information on licensing a Purdue innovation, contact the Office of Technology Commercialization at otcip@prf.org.

Cellular origin is well explained by the "endosymbiotic theory," which famously states that higher organisms called "eukaryotes" have evolved from more primitive single-celled organisms called "prokaryotes." This theory also explains that mitochondria--energy-producing factories of the cell--are actually derived from prokaryotic bacteria, as part of a process called "endosymbiosis." Biologists believe that their common ancestry is why the structure of mitochondria is "conserved" in eukaryotes, meaning that it is very similar across different species--from the simplest to most complex organisms. Now, it is known that as cells divide, so do mitochondria, but exactly how mitochondrial division takes place remains a mystery. Is it possible that mitochondria across different multicellular organisms--owing to their shared ancestry--divide in an identical manner? Considering that mitochondria are involved in some of the most crucial processes in the cell, including the maintenance of cellular metabolism, finding the answer to exactly how they replicate could spur further advancements in cell biology research.

In a new study published in Communications Biology, a group of scientists at Tokyo University of Science, led by Prof Sachihiro Matsunaga, wanted to find answers related to the origin of mitochondrial division. For their research, Prof Matsunaga and his team chose to study a type of red alga--the simplest form of a eukaryote, containing only one mitochondrion. Specifically, they wanted to observe whether the machinery involved in mitochondrial replication is conserved across different species and, if so, why. Talking about the motivation for this study, Prof Matsunaga says, "Mitochondria are important to cellular processes, as they supply energy for vital activities. It is established that cell division is accompanied by mitochondrial division; however, many points regarding its molecular mechanism are unclear."

The scientists first focused on an enzyme called Aurora kinase, which is known to activate several proteins involved in cell division by "phosphorylating" them (a well-known process in which phosphate groups are added to proteins to regulate their functions). By using techniques such as immunoblotting and kinase assays, they showed that the Aurora kinase in red algae phosphorylates a protein called dynamin, which is involved in mitochondrial division. Excited about these findings, Prof Matsunaga and his team wanted to take their research to the next level by identifying the exact sites where Aurora kinase phosphorylates dynamin, and using mass spectrometric experiments, they succeeded in identifying four such sites. Prof Matsunaga says, "When we looked for proteins phosphorylated by Aurora kinase, we were surprised to find dynamin, a protein that constricts mitochondria and promotes mitochondrial division."

Having gained a little more insight into how mitochondria divide in red algae, the scientists then wondered if the process could be similar in more evolved eukaryotes, such as humans. Prof Matsunaga and his team then used a human version of Aurora kinase to see if it phosphorylates human dynamin--and just as they predicted, it did. This led them to conclude that the process by which mitochondria replicate is very similar in different eukaryotic organisms. Prof Matsunaga elaborates on the findings by saying, "Using biochemical in vitro assays, we showed that Aurora kinase phosphorylates dynamin in human cells. In other words, it was found that the mechanism by which Aurora kinase phosphorylates dynamin in the mitochondrion is preserved from primitive algae to humans."

Scientists have long pondered over the idea of mitochondrial division being conserved in eukaryotes. This study is the first to show not only the role of a new enzyme in mitochondrial replication but also that this process is similar in both algae and humans, hinting towards the fact that their common ancestry might have something to do with this. Prof Matsunaga concludes by talking about the potential implications of this study, "Since the mitochondrial fission system found in primitive algae may be preserved in all living organisms including humans, the development of this method can make it easier to manipulate cellular activities of various organisms, as and when required."

As it turns out, we have much more in common with other species than we thought, and part of the evidence lies in our mitochondria!

Honoring a feat that was once considered impossible, Science has named the Event Horizon Telescope's image of a supermassive black hole as its 2019 Breakthrough of the Year. The image reveals one of the darkest and most elusive phenomena in the known universe. "This was a great year for science, but what could be more wondrous than actually seeing a black hole? It sounds like magic, but it was really an astonishing feat of teamwork and technology," says Tim Appenzeller, Science's news editor. Black holes are immensely dense cosmic objects with gravity so strong that they capture and consume everything surrounding them, including light. Since they reflect no light, black holes often hide in plain sight, perfectly camouflaged against the inky black of the void. However, by imaging the cloud of hot, brightly glowing gas that surrounds it, the EHT team of more than 200 scientists was able to capture the silhouette of the super massive black hole that lies at the center of Messier 87 (M87), a galaxy nearly 55 million light-years from Earth. While massive--M87's black hole weighs as much as 6.5 billion suns--it is small by galactic standards at roughly the size of our Solar System. "I'm still kind of stunned," said Roger Blandford, a Stanford University astrophysicist. "I don't think any of us imagined the iconic image that was produced." The historic image of the distant stellar object also captured the minds and imaginations of people world-wide - from front-page international news stories to internet memes - and quickly became the most downloaded image in the history of the National Science Foundation's website. Currently, plans are underway for more observations with even greater resolution; "this year's triumph is the beginning, not the culmination, of this research project, said Blandford.