Culture

URBANA, Ill. - Conflict over resource extraction is rampant in sub-Saharan Africa, with small-scale miners violently pitted against multinational mining corporations - and the state security forces that protect them - for access. Attempts to solve the problem by imposing Western environmental systems and regulations aren't working. But it's not for the reasons most experts might suspect, according to a new Illinois study.

"My research really pushes back against the idea that African regulators are corrupt or inept. They're actually implementing global governance standards exactly the way they should. And that's what's having the negative impact," says McKenzie Johnson, assistant professor in the Department of Natural Resources and Environmental Sciences at the University of Illinois, and author of the World Development study.

Johnson says resource conflicts in industrializing countries were historically seen by the international environmental community as the result of inadequate or dysfunctional environmental governance or regulation. There was a push, beginning in the 1970s, to build local "green governance" systems, modeled after the Environmental Protection Agency in the U.S. and similar entities in Europe.

However, it quickly became clear that simply plunking down Western green governance systems in these contexts wasn't working. Johnson explains.

"The international community recognized there are big cultural differences between western and African societies. Researchers argued that we could bridge the divide by building the capacity of domestic governance officials to translate global institutions so they make sense in a local context.

"What's actually happening is these domestic-level 'translators' have become part of this global system of governance. They go to all the meetings, work with organizations like the World Bank, and essentially become part of that architecture. Through this socialization process, they come to perceive Western systems are the correct way to govern natural resources and environment," she says. "So there is, in fact, no translation."

This means that environmental regulation is applied as is without considering the extent to which domestic producers can cope with the new rules.

Johnson bases her conclusion on months of work in Ghana and Sierra Leone, interviewing international development agents, regulators and other government officials, as well as local community groups. Without the benefit of "translation" between these different social systems, small-scale, local miners argued that centralized, bureaucratic processes, such as the process to obtain a mining license, are too difficult.

"If you're a small-scale or artisanal producer, you've got this mountain of paperwork to get through. Generally, you have to go to the capital city, and that could be days away. Even if you succeed in getting the licenses and finding land that's not occupied by a multinational corporation, then you have to abide by all these compliance standards that are really difficult," Johnson says. "There's no recognition of different levels of capability or the fact that this is a central livelihood for a lot of these miners."

According to Johnson, these issues are difficult to resolve because exclusive rules tend to benefit multinational companies. "Large companies are able to get through these processes a lot faster and easier because they have their own regulatory staff. As a result, regulation helps consolidate ownership of resources and becomes very exclusive. That's created a sense that the system is really unfair, and rigged against the little guy."

That sense that the rules are too hard to follow leads many local miners to go around the system and mine without proper licensing, Johnson says. When that happens on sites where multinational companies are already operating, violent conflict breaks out. And since the local miners are acting illegally, the government supports the multinationals.

Johnson isn't arguing against the benefits of green governance in sub-Saharan Africa. She notes that current systems have likely protected these countries from exploitation by multinational companies. However, she suggests that we should think about how to mitigate the unequal impacts of green rules within African contexts.

"I think you potentially need a more flexible system that accounts for differences between multinationals and artisanal and small-scale actors. There needs to be at least some recognition of the barriers different actors face, and a lot more inclusive conversation about these rules, what's legitimate, what's not, as well as potentially including indigenous traditions that states like the U.S. wouldn't feel comfortable with," she says.

The secret to making clothing practically indestructible could be the same thing that makes us grow out of it: sugar.

A new discovery from the University of Virginia School of Medicine reveals how sugars could be used to make almost indestructible cloth and other materials. Nature figured it out long ago, but the answer has been hidden away in bubbling baths of acid.

Amazing Extremophiles

In certain acidic hot springs, even volcanic hot springs, live ancient single-celled organisms that can exist in conditions far too extreme for most forms of life. They have tiny appendages called pili that are so tough that they resisted UVA scientists' numerous efforts to break them apart to learn their secrets. "We were unable to take these things apart in boiling detergent. They just remained absolutely intact," said researcher Edward H. Egelman, PhD, of UVA's Department of Biochemistry and Molecular Genetics. "So we then tried much harsher treatments, including boiling them in lye, which is sodium hydroxide. Nope."

The researchers tried several other approaches before throwing up their hands and turning to cryo-electron microscopy, which allows them to image submicroscopic things almost down to individual atoms. What they found was shocking. "There's just a huge amount of sugar covering the entire surface of these filaments in a way that has never been seen before," Egelman said. "These bugs have devised a way to just use massive amounts of sugar to cover these filaments and make them resistant to the incredible extremes of the environment in which they live."

You might liken the sugar coating to a hard sugar shell on a candy apple. The outer sugar shell is much harder than what it surrounds. In this case, though, the sugars were arranged in such a stable fashion that even acid can't dissolve them.

"These pili, which are protein filaments, normally would be very sensitive to heat, acid and enzymes, but coating it in sugars make it almost indestructible," Egelman explained. "There's a lot of evidence showing that adding small numbers of sugars can increase the stability of drugs and other protein structures, but no one, as far as we know, has ever seen this massive amount ... to the point where something is almost indestructible."

People can take a lesson from nature's design to manufacture products that are similarly sturdy, Egelman said. Take a protein such as wool, say, and coat it in a special arrangement of sugars and you could make amazingly durable clothing, carpet or even building materials. "Proteins are pretty sturdy and resilient, but with this type of covering of sugar, they would be much more stable, even more resilient," Egelman said. "They could have lots of uses."

The discovery is but the latest for Egelman, whose many contributions to his field recently earned him election to the National Academy of Sciences, one of the highest honors a scientist can receive.

LA JOLLA--(June 27, 2019) There are hundreds of thousands of distinct colors and shapes that a person can distinguish visually, but how does the brain process all of this information? Scientists previously believed that the visual system initially encodes shape and color with different sets of neurons and then combines them much later. But a new study from Salk researchers, published in Science on June 27, 2019, shows that there are neurons that respond selectively to particular combinations of color and shape.

"New genetic sensors and imaging technologies have allowed us to more thoroughly test the link between visual circuits that process color and shape," says Edward Callaway, senior author and professor in Salk's Systems Neurobiology Laboratory. "These findings provide valuable insight about how visual circuits are connected and organized in the brain."

Similar to a digital camera sensor, light-sensitive cells in the eye (photoreceptors) detect wavelengths of light within specific ranges and at particular locations. This information then travels through the optic nerve to neurons in the visual cortex that interpret the information and begin to decipher the contents of the picture. Scientists long thought that color and shape were extracted separately and then combined only at the highest brain centers, but the new Salk research shows that they are combined much earlier.

"The goal of our study was to better understand how the visual system processes colors and shapes of visual stimuli," says co-first author Anupam Garg, who is a University of California San Diego MD/PhD student in the Callaway lab. "We wanted to apply new imaging techniques to answer these longstanding questions about visual processing."

The researchers used imaging technology combined with genetically expressed sensors to study the function of thousands of individual neurons involved in processing color and shape in the primary visual cortex. During long recording periods, roughly 500 possible combinations of color and shape were tested to find the stimulus that best activated each visually-responsive neuron.

The team found that visual neurons selectively responded to color and shape along a continuum--while some neurons were only activated by either a specific color or shape, many other neurons were responsive to a particular color and shape simultaneously, contrary to long-held notions about how visual processing works.

"Our brain encodes visual information efficiently using circuits that are smartly designed. Contrary to what is taught in the classroom--that color and form are processed separately in the early visual cortex and then integrated later by unknown mechanisms--the brain encodes color and form together in a systematic way," says Peichao Li, co-first author and postdoctoral fellow in the Callaway lab.

"For the last 20 years, I have wanted to know how the visual system processes color, so this finding is truly exciting for me," says Callaway, who holds the Vincent J. Coates Chair in Molecular Neurobiology. "This discovery lays a foundation for understanding how neural circuits make the computations that lead to color vision. We look forward to building on these findings to determine how the neurons in the visual cortex work together to extract colors and shapes."

A happy cell is a balanced cell, but for every stupendously twisted protein it creates, it must tear the old ones asunder. That means untangling a convoluted pretzel-like mass for recycling. Cdc48 plays a critical role in unraveling the spent proteins.

"Cdc48 is the swiss army knife of the cell and can interact with so many different substrates," said Peter Shen, Ph.D., assistant professor in Biochemistry at University of Utah Health and senior author on the paper. "Until now we didn't have an understanding exactly of how it works."

Shen led a multi-institutional team of researchers to identify key structures of Cdc48 to visualize its undulations as it unfolds proteins. The results are available online in the June 27 issue of Science.

"We set out to do this because we care how molecular machines work," said Shen. "We decided to hone-in on Cdc48 due to clinical relevance."

For years, researchers have known that a single-point mutation in Cdc48 can cascade into serious diseases, including amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease type 2Y.

"Human Cdc48 is linked to multiple diseases and is the target of efforts to develop therapeutics for the treatment of cancers," said Christopher Hill, DPhil., distinguished professor of Biochemistry at U of U Health and co-corresponding author on the study.  "The structure that we have determined can be used to advance efforts to develop more effective inhibitors and therapeutics."

In the study, the research team purified Cdc48 directly from yeast cells (Saccharomyces cerevisiae) and took snapshots of the purified particles in different configurations after it was flash frozen using cryogenic electron microscopy (cryo-EM).

"The cells are already doing the hard work for us by making these complexes," Shen said. "Because this method is so fast, we have captured Cdc48 in the act of unfolding a protein substrate."

Using this approach, the research team demonstrated how Cdc48 unfolds the protein by threading it through a central pore of the complex, using a hand-over-hand conveyor-like movement. The recycled tangle they were imaging was a mystery until collaborators at Brigham Young University applied mass spectrometry proteomics to the same harvested complex to unmask the anonymous proteinan inactive protein phosphatase 1 complex.

Shen believes these results are applicable to human cells, because Cdc48 is highly conserved.

"We believe the structure we solved here will look very similar to what our bodies are expressing right now," he said.

The research team was unable to visualize the entire complex because Cdc48 interacts with multiple binding partners almost simultaneously. This efficient multitasking blurs the reconstruction; however, Shen wants to continue to explore how Cdc48 manages to bind with so many partners at roughly the same time.

"The coolest part is this [work] demonstrates that we can take a protein directly out of host cells and image them in their native state," Shen said. "I think this is the future of the cryo-EM field."

Based on careful study of fossilized teeth, scientists Keegan Melstom and Randall Irmis at the Natural History Museum of Utah at the University of Utah have found that multiple ancient groups of crocodyliforms--the group including living and extinct relatives of crocodiles and alligators--were not the carnivores we know today, as reported in the journal Current Biology on June 27. In fact, the evidence suggests that a veggie diet arose in the distant cousins of modern crocodylians at least three times.

"The most interesting thing we discovered was how frequently it seems extinct crocodyliforms ate plants," said Keegan Melstrom, (@gulosuchus) a doctoral student at the University of Utah. "Our study indicates that complexly-shaped teeth, which we infer to indicate herbivory, appear in the extinct relatives of crocodiles at least three times and maybe as many as six."

All living crocodylians possess a similar general body shape and ecology to match their lifestyle as semiaquatic generalist carnivores, which includes relatively simple, conical teeth. It was clear from the start of the study that extinct species showed a different pattern, including species with many specializations not seen today. One such specialization is a feature known as heterodonty: regionalized differences in tooth size or shape.

"Carnivores possess simple teeth whereas herbivores have much more complex teeth," Melstrom explained. "Omnivores, organisms that eat both plant and animal material, fall somewhere in between. Part of my earlier research showed that this pattern holds in living reptiles that have teeth, such as crocodylians and lizards. So these results told us that the basic pattern between diet and teeth is found in both mammals and reptiles, despite very different tooth shapes, and is applicable to extinct reptiles."

To infer what those extinct crocodyliforms most likely ate, Melstrom and his graduate advisor, chief curator Randall Irmis, compared the tooth complexity of extinct crocodyliforms to those of living animals using a method originally developed for use in living mammals. Overall, they measured 146 teeth from 16 different species of extinct crocodyliforms.

Using a combination of quantitative dental measurements and other morphological features, the researchers reconstructed the diets of those extinct crocodyliforms. The results show that those animals had a wider range of dental complexities and presumed dietary ecologies than had been appreciated previously.

Plant-eating crocodyliforms appeared early in the evolutionary history of the group, the researchers conclude, shortly after the end-Triassic mass extinction, and persisted until the end-Cretaceous mass extinction that killed off all dinosaurs except birds. Their analysis suggests that herbivory arose independently a minimum of three times, and possibly six times, in Mesozoic crocodyliforms.

"Our work demonstrates that extinct crocodyliforms had an incredibly varied diet," Melstrom said. "Some were similar to living crocodylians and were primarily carnivorous, others were omnivores and still others likely specialized in plants. The herbivores lived on different continents at different times, some alongside mammals and mammal relatives, and others did not. This suggests that an herbivorous crocodyliform was successful in a variety of environments!"

Melstrom says they are continuing to reconstruct the diets of extinct crocodyliforms, including in fossilized species that are missing teeth. He also wants to understand why the extinct relatives of crocodiles diversified so radically after one mass extinction but not another, and whether dietary ecology could have played a role.

Bottom Line: An observational study suggests the U.S. Preventive Services Task Force (USPSTF) lung cancer screening guidelines may be too conservative for African American smokers and that some eligibility criteria changes could result in more screenings of African American smokers at high risk for lung cancer. The study looked at new lung cancer cases in a predominantly low-income and African American population group to assess their eligibility for lung cancer screening using the USPSTF criteria. The USPSTF routinely makes recommendations about the effectiveness of preventive care services. This study included 48,364 adults who ever smoked (67% were African American) and 1,269 new lung cancers were identified. Among the smokers, 17% of African  American smokers were eligible for USPSTF screening compared with 31% of white smokers. The lower percentage of lung cancer cases eligible for screening among African American smokers was largely associated with fewer smoking pack-years (a measure of smoking) among African American smokers compared with white smokers. African Americans tend to smoke fewer cigarettes per day and tend to have a lower overall smoking pack-year history compared with white smokers. These study results suggest that lowering the smoking pack-year eligibility requirement from 30 to 20 pack years for African American smokers could increase the number of African American smokers eligible for screening. In addition, reducing the minimum age criterion for screening to 50 for African American smokers could further increase eligibility. The average age of a lung cancer diagnosis tends to be earlier for African American smokers compared with white smokers. This study has limitations to consider, including that smoking was self-reported and authors didn't have information about actual lung cancer screening use.

Financial crises not only result in severe disruptions to the economic system, they also affect people's life satisfaction. A new study by Martin Luther University Halle-Wittenberg (MLU) and the Halle Institute for Economic Research (IWH) shows that weaker members of society are more affected by increased uncertainty during crisis times, even if they may not be speculating on the stock market themselves. This could potentially also lower their propensity to consume, thereby intensifying the impact of a financial crisis. The study was recently published in "The B.E. Journal of Economic Analysis & Policy".

Higher uncertainty on financial markets has a direct impact on people's life satisfaction. While this statement might seem rather obvious, it has now been scientifically proven in an empirical analysis focusing on recent crisis developments across European countries. The study was led by Assistant Professor Lena Tonzer at MLU and IWH. "This phenomenon, that people are less satisfied with their life in uncertain times, is heightened during financial crises," says Lena Tonzer. And: "The effect mainly impacts the weaker members of society." In other words, the unemployed and less well educated suffer more from uncertain financial markets, even if they themselves do not speculate in the stock market.

Some of Tonzer's empirical analysis was based on data from the Eurobarometer Surveys, a public opinion survey commissioned by the European Commission at regular intervals. One key objective is to measure perceptions about EU-wide policies across the member states. The survey also includes questions about life satisfaction. This enabled Tonzer to establish that the effect of personal dissatisfaction was relatively higher in times of financial uncertainty in those countries most severely affected by the financial and sovereign debt crisis: more precisely in Spain, Portugal, Italy, Greece and Ireland.

Such a rigorous analysis is not an end in itself: "It is important to identify which population groups are hit worst. This is the only way to counteract this with political measures," explains Tonzer. There was also evidence that the effect was less pronounced in countries with an effective state-supported safety net. This leads to several conclusions: "There are effective ways of exerting political influence to counteract negative social effects. These should be used to protect the weaker members of society."

In order to prevent financial crises from the outset or to mitigate the effects of a downturn, macroprudential policies can be introduced, such as the anti-cyclical capital buffer. The aim of this instrument is that banks accumulate more equity capital in good times so that they have a buffer in bad times to absorb losses more easily and so that they can continue to grant loans to the real economy. The Financial Stability Committee of the Federal Ministry of Finance recently recommended that the Federal Financial Supervisory Authority (BaFin) shall activate this capital buffer in Germany.

Another important point is that, while a social security system is important, it should not be expanded at the expense of an increase in government debt. The reason is that, in uncertain times, life satisfaction tends to decline more in countries with higher public debt, which in turn would further burden the system and increase people's fears. "If they are more afraid because their future seems more uncertain, they will probably buy less and be less willing to invest compared to economically stable times. The result would be another downward spiral", Tonzer concludes. Based on her analysis, she feels certain that "It makes sense to look at these soft factors, because everything is interconnected."

San Diego, CA - June 27, 2019 - Meal delivery drivers bringing food to homebound seniors can be an effective early-warning system for health and safety problems, according to a new study published in the Journal of the American Geriatrics Society by researchers at the West Health Institute, Brown University and Meals on Wheels America.

The study, titled "Leveraging Home-Delivered Meal Programs to Address Unmet Needs for At-Risk Older Adults: Preliminary Data," was designed to test the feasibility of leveraging routine meal delivery service in two home delivered meal programs at Meals on Wheels San Diego County and Meals on Wheels Guernsey County, Ohio to proactively identify changes in older adult meal recipients' (clients') health, safety and well-being and address unmet needs.

In the study, meal delivery drivers were trained to use a mobile application to submit electronic alerts when they had a concern or observed a change in a client's condition. Alerts were received by care coordinators, who followed up with clients to offer support and help connect them to health and community services.

Over a 12-month period, drivers submitted a total of 429 alerts for 189 clients across two pilot sites. The most frequent alerts were submitted for changes in health (56%), followed by self-care or personal safety (12%) and mobility (11%). On follow-up, a total of 132 referrals were issued, with most referrals for self?care (33%), health (17%), and care management services (17%). Focus groups conducted with drivers indicated that most found the mobile application - "Mobile Meals," part of Accessible Solutions, Inc.'s ServTracker software - easy to use and valued change of condition monitoring as an important contribution.

A special editor's note accompanying the publication highlighted the potential for this program to improve the health and safety of homebound seniors.

"As healthcare systems struggle to address the social determinants of health, this innovative Meals on Wheels model may provide part of the solution," said Dr. Michael L. Malone, a section editor in models of geriatric care, quality of improvement, and program dissemination with the Journal of the American Geriatrics Society. "As leaders in geriatric medicine, we should champion social programs (such as Meals on Wheels) that meet the needs of vulnerable individuals in our communities. In retrospect, our core business is to help the whole person, whose healthcare needs are intertwined with his/her social needs."

West Health and Meals on Wheels America recently announced plans to expand this successful research program to include up to 30 Meals on Wheels sites across the country, helping ensure the wellness of an estimated 40,000 seniors.

"By collaborating with Meals on Wheels America, we've developed a safe, cost-effective and scalable program to preemptively identify and address concerns that too often result in deterioration of a senior's medical condition or pose a major safety risk," said Dr. Zia Agha, chief medical officer at West Health. "We're excited learnings from this research program are now being implemented across the country within Meals on Wheels America's expanded program that will positively impact as many seniors as possible."

In a recent study with 3 to 7-year-old children provided an example of how children's daily living environment and motor skills are closely related in the Finnish context. The main finding revealed that residential density is related to children's motor skills, engagement in outdoor play and organised sports. It was found that Finnish children living in the countryside spent more time outdoors and had better motor skills than their age peers in the metropolitan area. On the other hand, children living in the metropolitan area participated the most in organised sports.

Motor skills comprise locomotor, object control and balance skills, all of which are present in everyday life tasks like running, climbing and drawing. Adequate motor skills enable participation in typical games and plays for different ages and developmental phases, for example, in running and ball games.

- In early childhood, the mastery of basic motor skills is one of the main developmental task of the child. Motor skills enable children to participate in various physical activities and physically active play. Mutual plays and games enable children to have friends to play with. Moreover, motor skills are also crucial when it comes to school adaptation, says PhD. student Donna Niemistö from the Faculty of Sport and Health Sciences, University of Jyväskylä.

Motor skills do not develop to an optimal level without practising. So far, we know that one out of ten children have delays in their motor development. These delays can complicate everyday tasks, such as putting clothes on, writing and riding a bike.

- Every child, with or without delays in motor skills, develops motor skills through repetition of the task. For the child's development, it is crucial that (s)he has an opportunity to try, play and practise spontaneously. The parental presence while moving assures the child that practising motor skills is important and safe. Therefore, for example, summertime is an excellent period to move as a family, as nature enables versatile experiences and stimuli for the child's motor development, explains Niemistö.

Time spent outdoors and participation in organised sports promote children's motor learning

The findings suggest that the time spent outdoors and participation in organised sports support motor development. In fact, Niemistö points out that opportunities for time spent outdoors and participation in organised sports are important in terms of equality in the society.

Children find outdoor environments stimulating and motivating - for example, large yards that provide opportunities to play and run. Indeed, free running and playing are important for the development of the locomotor skills, such as walking, running, climbing, galloping and jumping. Furthermore, large spaces and playing areas are also crucial in practising object control skills.

- When a child feels as competent in a given motor task, (s)he will practise more, and through the increased repetition, (s)he will gain better motor skills, underlines Niemistö.

When planning the environment, one should take into consideration the safety, versatility and independency of the child's opportunity to move around in an age appropriate way. Due to common access, Finnish children have free access to environment and the opportunities it offers. However, to enhance equality within the country, we should recognize the differences in the environments and develop them equally and, consequently, enhance children's equal motor skill development possibilities.

The Skilled Kids study, conducted at the University of Jyväskylä from 2015 to 2017, had a geographically representative study sample of 945 children and their families from 37 different childcare centres in Finland. Children's motor skills were assessed with internationally well-known indicators, which assessed locomotor and object control skills. The time spent outdoors and participation in organized sports were enquired on a parental questionnaire. Based on the residential density, six of the childcare centres were located in the metropolitan area, 17 in cities, seven in rural areas and, finally, seven in the countryside.

Infants of women with a short-term education are more likely to die within the first year of life. In more than half of cases, the cause of death is premature childbirth and low foetal weight. This is shown by research from Aarhus University and Aarhus University Hospital.

In Denmark, four out of 1,000 newborn babies die before reaching their first birthday. Now, a new research project shows that women with short-term (primary and lower secondary education less than nine years) or no education have an increased risk of their child dying during the first year. Premature birth and low foetal weight can explain 55-60 per cent of cases.

Yongfu Yu and Jiong Li from Aarhus University and Aarhus University Hospital are behind the study.

"Despite the fall in child mortality in recent decades, there still remains a socio-economic imbalance in the infant mortality rate. Something needs to be done about that," Jiong Li says.

The results have just been published in PLoS Medicine. They are based on a national population study of 1.99 million children born in Denmark in the years 1981-2015.

"To reduce the risk of premature childbirth and low foetal weight will be helpful. One way among others of doing this is by increased focus on improving the health of socially and financially disadvantaged women before and during pregnancy," says Yongfu Yu.

He hopes that the results can contribute to the prevention of premature deaths in infants.

"Even in a welfare society like Denmark, pregnant women with short-term education need more resources to address social challenges in order to improve the health of infants in general and reduce child mortality in particular," says Yongfu Yu.

Prof. HU Junjie from the Institute of Biophysics of the Chinese Academy of Sciences and his collaborators reported that the endoplasmic reticulum (ER) fusogen atlastin (ATL) was involved in regulating cargo mobility and COPII formation in the ER. Their finding, published in PNAS on June 25, provides important insight into the physiological role of the tubular ER network.

In eukaryotic cells, the ER forms a complex network of continuous sheets and tubules. Tubules are shaped by a class of integral membrane proteins, the reticulons and REEPs, and subsequently connected in the form of 3-way junctions by dynamin-like GTPase atlastin.

Deletion or mutation of ATL in mammalian cells results in long unbranched ER tubules indicative of a lack of fusion between tubules, and mutation of human ATL1 is linked to hereditary spastic paraplegia. Prof. HU's previous work demonstrated that ATL and its homologs mediate fusion of the ER, particularly the tubular network, but the specific physiological functions of the tubular ER networks remain unclear.

After folding and proper modification, cargo proteins exited the ER through COPII coated vesicles. Researchers found that in ATL-deleted cells, COPII formation was drastically reduced in the cell periphery, and ER export became defective.

While ER exit site initiation was not affected, many of the sites failed to recruit COPII subunits. Subsequently, in vitro vesicular release assay revealed that the efficiency of cargo packaging into COPII vesicles was significantly reduced in cells lacking ATLs.

Further studies found that cargo was less mobile in the ER in the absence of ATL. Interestingly, the cargo mobility and COPII formation could be restored by ATL R77A, which was capable of tethering, but not fusing, ER tubules.

These findings suggest that ATL-mediated membrane tethering plays a critical role in maintaining the necessary mobility of ER contents to allow efficient packaging of cargo proteins into COPII vesicles. It has been shown that membrane tension affects mobility of membrane components. The activity of ATL, particularly in membrane tethering, may contribute to regulating membrane tension in the ER.

In a pilot study of 14 older adults with mild cognitive problems suggestive of early Alzheimer's disease, Johns Hopkins Medicine researchers report that a high-fat, low-carbohydrate diet may improve brain function and memory.

Although the researchers say that finding participants willing to undertake restrictive diets for the three-month study -- or partners willing to help them stick to those diets -- was challenging, those who adhered to a modified Atkins diet (very low carbohydrates and extra fat) had small but measurable improvements on standardized tests of memory compared with those on a low-fat diet.

The short-term results, published in the April issue of the Journal of Alzheimer's Disease, are far from proof that the modified Atkins diet has the potential to stave off progression from mild cognitive impairment to Alzheimer's disease or other dementias. However, they are promising enough, the researchers say, to warrant larger, longer-term studies of dietary impact on brain function.

"Our early findings suggest that perhaps we don't need to cut carbs as strictly as we initially tried. We may eventually see the same beneficial effects by adding a ketone supplement that would make the diet easier to follow," says Jason Brandt, Ph.D., professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine. "Most of all, if we can confirm these preliminary findings, using dietary changes to mitigate cognitive loss in early-stage dementia would be a real game-changer. It's something that 400-plus experimental drugs haven't been able to do in clinical trials."

Brandt explains that, typically, the brain uses the sugar glucose -- a product of carbohydrate breakdown -- as a primary fuel. However, research has shown that in the early stage of Alzheimer's disease the brain isn't able to efficiently use glucose as an energy source. Some experts, he says, even refer to Alzheimer's as "type 3 diabetes."

Using brain scans that show energy use, researchers have also found that ketones -- chemicals formed during the breakdown of dietary fat -- can be used as an alternative energy source in the brains of healthy people and those with mild cognitive impairment. For example, when a person is on a ketogenic diet, consisting of lots of fat and very few sugars and starches, the brain and body use ketones as an energy source instead of carbs.

For the current study, the researchers wanted to see if people with mild cognitive impairment, often an indicator of developing Alzheimer's disease, would benefit from a diet that forced the brain to use ketones instead of carbohydrates for fuel.

After 2 1/2 years of recruitment efforts, the researchers were able to enroll 27 people in the 12-week diet study. There were a few dropouts, and so far, 14 participants have completed the study. The participants were an average age of 71. Half were women, and all but one were white.

To enroll, each participant required a study partner (typically a spouse) who was responsible for ensuring that the participant followed one of two diets for the full 12 weeks. Nine participants followed a modified Atkins diet meant to restrict carbs to 20 grams per day or less, with no restriction on calories. The typical American consumes between 200 and 300 grams of carbs a day. The other five participants followed a National Institute of Aging diet, similar to the Mediterranean diet, that doesn't restrict carbohydrates, but favors fruits, vegetables, low- or fat-free dairy, whole grains and lean proteins such as seafood or chicken.

The participants and their partners were also asked to keep food diaries. Prior to starting the diets, those assigned to the modified Atkins diet were consuming about 158 grams of carbs per day. By week six of the diet, they had cut back to an average of 38.5 grams of carbs per day and continued dropping at nine weeks, but still short of the 20-gram target, before rising to an average of 53 grams of carbs by week 12. Participants on the National Institute of Aging diet continued to eat well over 100 grams of carbs per day.

Each participant also gave urine samples at the start of the dietary regimens and every three weeks up to the end of the study, which were used to track ketone levels. More than half of the participants on the modified Atkins diet had at least some ketones in their urine by six weeks into the diet until the end; as expected, none of the participants on the National Institute of Aging control diet had any detectable ketones.

Participants completed the Montreal Cognitive Assessment, the Mini-Mental State Examination and the Clinical Dementia Rating Scale at the start of the study. They were tested with a brief collection of neuropsychological memory tests before starting their diets and at six weeks and 12 weeks on the diet. At the six-week mark, the researchers found a significant improvement on memory tests, which coincided with the highest levels of ketones and lowest carb intakes.

When comparing the results of tests of delayed recall -- the ability to recollect something they were told or shown a few minutes earlier -- those who stuck to the modified Atkins diet improved by a couple of points on average (about 15% of the total score), whereas those who didn't follow the diet on average dropped a couple of points.

The researchers say the biggest hurdle for researchers was finding people willing to make drastic changes to their eating habits and partners willing to enforce the diets. The increase in carbohydrate intake later in the study period, they said, suggests that the diet becomes unpalatable over long periods.

"Many people would rather take a pill that causes them all kinds of nasty side effects than change their diet," says Brandt. "Older people often say that eating the foods they love is one of the few pleasures they still enjoy in life, and they aren't willing to give that up."

But, because Brandt's team observed promising results even in those lax with the diet, they believe that a milder version of the high-fat/low-carb diet, perhaps in conjunction with ketone supplement drinks, is worth further study. As this study also depended on caregivers/partners to do most of the work preparing and implementing the diet, the group also wants to see if participants with less severe mild cognitive impairment can make their own dietary choices and be more apt to stick to a ketogenic diet.

A standardized modified Atkins diet was created and tested at Johns Hopkins Medicine in 2002, initially to treat some seizure disorders. It's still used very successfully for this purpose.

According to the Alzheimer's Association, about 5.8 million Americans have Alzheimer's disease, and by 2050 the number is projected to increase to 14 million people.

Osaka, Japan - The early development of embryos is not well understood. One necessary stage is the formation of the blastocyst, a collection of cells present by about 4 days after fertilization of the egg, before implantation in the uterus. From that tiny collection of cells, all the different cells in the body must be created. Accordingly, there need to be mechanisms in the blastocyst to ensure normal gene expression and cell differentiation; those regulatory mechanisms are still largely unknown.

It is known that the proteins in the tumor-suppression "Hippo pathway" act in cells throughout the body to regulate normal organ growth and tissue regeneration. These proteins ensure that organs reach the sufficient size, while countering excessive enlargement. Therefore, researchers have theorized that Hippo-pathway proteins contribute to regulation of normal blastocyst development. That theory was confirmed recently when Masakazu Hashimoto and Hiroshi Sasaki, of the Graduate School of Frontier Biosciences at Osaka University, demonstrated that the Hippo-pathway proteins TEAD and YAP serve an important regulatory function in blastocysts. Together, these proteins support pluripotency (i.e., the ability to become any type of cell) in the blastocyst before implantation.

In their study, published in the journal Developmental Cell, Drs. Hashimoto and Sasaki used genetically modified mouse cells to alter the amounts and timing of TEAD activation during blastocyst formation. Results showed that accumulation of YAP in cell nuclei activated TEAD and, subsequently, activated transcription factor MYC. This activation sequence then induces a previously unknown process of cell competition within the blastocyst.

"We were able to measure levels of activated TEAD-YAP in the epiblast (a layer of the blastocyst) of day 4 after fertilization, and show that levels differed between cells. Higher levels of TEAD are associated with greater pluripotency, so cells with low TEAD, and thus low pluripotency, must be eliminated from the epiblast," says corresponding author Dr. Sasaki.

That elimination is achieved when cell competition, through encountering neighboring cells with higher levels of TEAD, induces apoptosis (cell self-destruction) in cells of low pluripotency.

First author Dr. Hashimoto adds that "Appropriate control of the Hippo pathway in epiblasts acts as a quality-control mechanism, ensuring that all cells have the maximum potential to develop into the many different cell types that are required for the growing embryo."

The information gained in this study could aid in improved induction of pluripotent stem cells, of potential use in various clinical trials, and in the maintenance of embryos for in-vitro fertilization.

(Boston)--Increasing the levels of the anti-aging protein hormone Klotho improves the neurological deficits and prolongs life span in an experimental model with Amyotrophic Lateral Sclerosis (ALS). In addition, brain immune cells called microglia play an important role in protecting the brain against inflammation and, likely, motor neuron loss in this model.

ALS or Lou Gehrig's disease, is a devastating neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive muscle atrophy and paralysis, which is fatal within three to five years of diagnosis.

Researchers from Boston University School of Medicine (BUSM) have previously shown that increasing Klotho protein levels is beneficial in experimental models of Alzheimer's disease and multiple sclerosis. "Here we now show that Klotho is also neuroprotective in an ALS model. Thus, increasing Klotho levels would be a logical treatment for age-related neurodegenerative and neuroinflammatory diseases," explained corresponding author Carmela Abraham, PhD, professor of biochemistry at BUSM.

Unfortunately, very few treatments are available to ALS patients today. "We propose that increasing the levels of the Klotho protein would significantly alleviate the neurologic manifestations, improve the quality of life and prolong life span in patients with ALS. If one was to extrapolate the results of this study, increasing Klotho by only 50 percent would prolong life by approximately 300 days."

According to Abraham, anything that increases Klotho levels is neuroprotective. For example, it has been shown that exercise increases Klotho. "This may be relevant for healthy individuals or patients newly diagnosed with ALS. Additionally, in the cases of familial ALS, family members who wish to be tested and discover that they are carriers of an ALS gene could start exercising or start Klotho boosting therapy, once it becomes available."

Water is a vital resource for people and the environment. One of the most important sources is groundwater which is renewed from precipitation or surface water. Population growth as well as agriculture and industry strongly influence the quantity and quality of groundwater. To be able to investigate groundwater resources more easily, cost-effectively and comprehensively than in the past, researchers at Karlsruhe Institute of Technology (KIT) have developed a new method with Australian colleagues which they are now unveiling in the Reviews of Geophysics journal.

According to the German Environment Agency, more than 70 percent of drinking water originates from groundwater in Germany alone. Production is increasing so rapidly across the world that groundwater levels are falling, quality is deteriorating and whole cities are facing groundwater-related subsidence. Therefore, it is important to explore subsurface properties for managing resources more sustainably.

"Current testing methods require active pumping of water from a specially designed water extraction well while observing the water level in other wells in the vicinity," says Dr. Gabriel Rau from the Institute of Applied Geosciences (AGW) at KIT. To do this, two or three people would need to set up a pump test and supervise measurements for an extended period of time. This method is very expensive, can last anywhere from a few hours to several months depending on the subsurface properties, and the result is only valid for the tested location. "Underground aquifers vary greatly in space, and it is much too expensive and intrusive to build extraction wells everywhere."

Together with the University of New South Wales (UNSW) in Sydney and the Deakin University in Melbourne, KIT has now developed a new method which evaluates information about tidal effects on groundwater levels. Similar to tides in the ocean, the groundwater level is affected by tidal forces, with the change in gravitation squeezing the porous rocks in the subsurface and causing measurable pressure changes. In addition, there are atmospheric tides which cyclically change subsurface pressure. "We can measure this change at low cost and using less complex procedures and fewer personnel to quantify subsurface properties," says Rau. Engineers require no special extraction wells for this but can place an automated water pressure data logger at a conventional groundwater measuring point. The pressure sensor then measures the groundwater level regularly for at least a month. Using the measurements, researchers can calculate the physical properties of the subsurface such as porosity, hydraulic conductivity and compressibility and translate the findings into the sustainable use of groundwater resources. "Since it is much cheaper to drill monitoring boreholes than to create entire wells, we can carry out measurements in more locations, significantly increasing the number and coverage of the subsurface properties calculated," says Rau.

The researchers have studied and summarized international studies and articles from various disciplines for their method: "We have seen that the recent advances in groundwater research show potential for much cheaper long-term groundwater studies," says Timothy McMillan from the Connected Waters Initiative Research Center at UNSW Sydney. "In our method we use a combination of engineering, science and maths, and the impact of tides on groundwater to calculate the subsurface properties." These findings can also contribute to predicting spatial and temporal fluctuations of the climate system and its impact on groundwater resources. "We are facing enormous challenges in the future. Our method makes it easier to investigate subsurface resources and therefore to manage them more sustainably," says Rau.