Culture

Cells regularly go through a process called autophagy - literally translated as 'self-eating' - which helps to destroy bacteria and viruses after infection.

When it works, this process counteracts neurodegenerative conditions such as dementia and Huntington's Disease, by getting rid of unwanted proteins and their resultant harm to cells.

But when autophagy fails or defects occur, it can give rise to such conditions.

Now new research by the University of Plymouth has shed light on the mechanisms behind autophagy and how it progresses - particularly relating to a process called liquid-liquid phase separation (LLPS).

The paper was published today (Wednesday 21 August) in Nature Communications, and could provide the first steps towards new treatments for neurodegenerative diseases.

What does the science tell us?

The clearance of cell wastes by autophagy is controlled by two things involving a protein called p62 - firstly, a chemical process that sees p62 bind a number of identical molecules together (called oligomerisation), and secondly, p62's separation of molecules within cell fluid. The demixing process is called liquid-liquid phase separation (LLPS).

It is crucial to clarify how p62 LLPS is regulated in cells, and scientists have discovered that the process is facilitated by another protein called DAXX.

The study is the first to shed light on this particular protein interaction and its subsequent roles in autophagy and cell protection.

Providing new insights into autophagy, the research helps clarify a key process that might be faltering in those who develop dementia conditions.

What the scientists say

The study was led by Dr Shouqing Luo and his research group from the University of Plymouth's Institute of Translational and Stratified Medicine (ITSMed), in collaboration with Fudan University, Shanghai and Thomas Jefferson University, Philadelphia.

Dr Luo, whose work primarily focuses on finding new autophagy pathways, as well as novel treatments for dementia diseases - using Huntington's Disease (HD) as a model - said: "By understanding more about autophagy and the details of the processes involved, we can identify what might be going wrong, and therefore where to target when it comes to tackling neurodegenerative diseases. This research is a major step in helping us to do that.

"The next step for us is to look at applying the science within human cells, so we can further clarify how the protein interaction and the new DAXX function are relevant to neurodegenerative conditions including HD, and whether we can target it to help prevent disease progression.

"HD is an inherited disease that causes the progressive breakdown of nerve cells in the brain. It has a broad impact on a person's functional abilities and currently there is no cure, so it's vital that we continue our work to find out how and why the disease develops."

PHILADELPHIA -- (Aug. 21, 2019) -- Contrary to the long-held view that semen can only act as a way to transmit HIV-1 from men to women, scientists at The Wistar Institute and the University of Puerto Rico found that frequent and sustained semen exposure can change the characteristics of the circulating and vaginal tissue immune cells that are targets for infection, reducing the susceptibility to a future infection. This finding, published in the journal Nature Communications, also provides a potential explanation as to why a small number of female sex workers worldwide continue to test negative for infection despite continuous high-risk sexual activity.

Research previously reported by the laboratory of Luis J. Montaner, D.V.M., D.Phil., the Herbert Kean, M.D., Family Professor and director of the HIV-1 Immunopathogenesis Laboratory at Wistar's Vaccine & Immunotherapy Center, together with investigators at the University of Puerto Rico, showed in a 2015 paper how continued semen exposure in female sex workers resulted in changes in the cervicovaginal tissue that predicted an increased resistance to HIV infection. The current study directly addressed if semen could be a factor in resistance.

"While HIV infection has been with us for more than 30 years, this is the first study that describes how semen exposure over time could result in local tissue changes that limit HIV infection in humans," said Montaner, who is the lead author of the new study. "Apart from defining a new factor that may regulate HIV transmission, this unexpected finding could directly impact the design of future HIV vaccine studies that commonly recruit female sex workers. Currently, condomless sex is assumed to only promote the likelihood of infection. Our observation, however, raises the hypothesis that frequent semen exposure may potentially reduce HIV transmission."

Edmundo N. Kraiselburd, Ph.D., professor at the University of Puerto Rico (UPR), co-directed this research project and supervised the use of non-human primates (NHP) from the Caribbean Primate Research Center. NHPs are a principal pre-clinical research model used to test prophylactic anti-HIV interventions.

"This research clearly shows the valuable information the macaque model can provide when used to study what may determine HIV infections in humans," said Kraiselburd.

In the study, animals were exposed to semen twice a week over 20 weeks with or without inactivated particles of the simian immunodeficiency virus (SIV is an HIV-like virus that infects primates and causes a disease similar to AIDS); after this conditioning period, they received low-dose intravaginal SIV challenges.

Semen-exposed animals showed a 42% decrease in the risk of infection. Scientists analyzed specific markers of immune activation in the cervicovaginal microenvironment and in the bloodstream. On circulating CD4+ cells, semen conditioning was associated with lower expression of the CCR5 receptor, which acts as a binding site for HIV to enter its host cells, supporting the observation of a lower susceptibility to SIV vaginal challenge. Furthermore, semen-conditioned animals had higher levels of the CCL5 cytokine, a natural HIV-suppressive factor, in the cervicovaginal compartment in response to SIV challenge.

Additionally, repeated semen exposure resulted in elevated cervicovaginal tissue levels of antiviral factors such as MX1, which also positively correlated with levels of IFN-epsilon. IFN-epsilon, which can be induced by semen and protects human cells from bacterial and viral pathogens, has direct anti-HIV properties and was described to be induced in tissues from sex workers in association with condomless sex.

Of note, semen-treated animals that remained uninfected after exposure to low viral amount became infected when subsequently challenged with high doses of virus, confirming that they were still susceptible to infection and that repeated semen exposure provides only partial protection and does not block HIV infection.

"Importantly, we show that semen exposure can promote host resistance but does not protect against infection," said Montaner. "Therefore, our data do not change the fact that prevention methods, such as condom use and PrEP (pre-exposure prophylaxis) remain our best strategies to prevent infection."

Johns Hopkins researchers report that prurigo nodularis (PN), a skin disease characterized by severely itchy, firm bumps on the skin, may be associated with other inflammatory skin disorders as well as systemic and mental health disorders. Compared with other skin diseases, however, not much is known about PN. While symptoms of PN can be managed, no cures exist. Researchers were looking to determine associated conditions that are more common in patients with PN, compared with similar patients without PN.

A report on the findings was published in the Journal of Investigative Dermatology.

"A lot of patients who have prurigo nodularis also have associated severe health conditions that need more immediate attention, and many of these PN patients may fall through the cracks," says dermatologist Shawn Kwatra, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine.

While skin conditions such as psoriasis and eczema are known to be caused by an overactive immune system, the underlying molecular cause of PN remains unknown because the disease has been understudied. Kwatra and colleagues then sought to learn more by first estimating how prevalent PN is in the United States.

As a starting point, Kwatra and team analyzed one of the largest national databases of insurance data in the U.S. (IBM MarketScan Commercial Claims and Encounters) between October 2015 and December 2016. They identified patients 18-64 years old with medical insurance who presented two or more insurance claims relating to PN, maintained for three months or more, and compared them with patients without PN, patients with atopic dermatitis and patients with psoriasis.

In their study, they identified 7,095 people with PN, 23,882 with atopic dermatitis without PN and 38,283 with psoriasis without PN. Based on these numbers, they calculated that more than 72 per 100,000 people are affected with PN, primarily females with an average age of 50 years.

"The real numbers may be higher than this because our data only included people with health insurance and between the ages of 18 and 64," says Johns Hopkins University School of Medicine fourth-year medical student Amy Huang.

According to The National Institutes of Health, PN may develop from other skin diseases or other health issues that may be common in families, and even environmental factors may place one at an increased risk of developing PN. Analyzing the data further, the team found that those with PN have increased risk of other conditions compared with people without PN, including HIV, kidney disease, non-Hodgkin's lymphoma and mental health disorders.

"We are eager to better understand PN because that will help in the management of our patients," says Kwatra. "Our goal is to inform other physicians about the frequency of PN-related associated conditions to guide an evidence-based, targeted diagnostic workup. Enhanced disease recognition and ongoing translational studies will provide further clues to the development of PN."

While there is no cure for PN, current treatment includes phototherapy, topical steroids and off-label management with immune suppressants and anticonvulsants. Kwatra says it's important for physicians to be well-informed about related conditions so PN can be properly diagnosed and managed.

Ongoing research initiatives include examining the patterns of PN in children and adults age 65 and over and how PN treatment affects these populations. Additional studies are ongoing by Kwatra's group to understand the molecular explanation of PN.

Further research is needed to clarify how chronic conditions such as atopic dermatitis, HIV, renal impairment and mental health conditions may contribute to the development of PN.

"With such a large population of people who have this neglected disease, we've only scratched the surface and are happy to take the lead with investigating this understudied condition," Kwatra says.

PULLMAN, Wash. - Round numbers can be powerful marketing tools, increasing people's sense of accomplishment as they work towards goals in areas like finances or weight loss, according to new Washington State University research.

"Most people have a preference for round numbers," said Kunter Gunasti, an assistant professor of marketing and international business at WSU's Carson College of Business. "Hitting a round number makes us feel more complete. This happens when we're taking tests, getting paid, leaving tips or pumping gas."

Many of us, for instance, would be more excited about receiving a $2,000 paycheck in Canadian currency than the U.S equivalent of $1,521, Gunasti said. And, being told that we've lost 10 kilograms might give us a greater feeling of achievement than hearing the identical amount expressed as 22 pounds.

New research by Gunasti and Timucin Ozcan, an associate marketing professor at James Madison University, demonstrates how effective round numbers can be in consumer marketing campaigns. Their work, which was published in the journal Marketing Letters, measures how consumers' feelings of accomplishment are influenced by changing the scales used to track progress.

Studies test effect of round numbers in wages, loyalty programs, video games

Gunasti and Ozcan said reaching a goal expressed in round numbers results in higher levels of customer satisfaction. That was particularly true when the final goal was still distant, the researchers said. Hitting intermediate targets expressed as round numbers increased customers' feeling of progress at low levels of achievement.

The researchers tested their theory in laboratory scenarios related to wages, loyalty programs and video games. In the scenarios, they manipulated the scales used to track progress.

People who were working towards a monthly earnings target felt better about their paychecks when their wages were expressed in round numbers.

Another scenario tracked customers' progress toward a free international flight through an airline loyalty program. People felt closer to earning the free flight when the currency tracking the rewards points was switched from British pounds to euros, allowing customers to hit a round number for an intermediate target toward the flight.

A third scenario looked at video games where participants were trying to earn up to 100 points. After three games, participants felt a greater sense of satisfaction from reaching 50 points than they did when they ended at 51 points.

'Don't be a slave to the decimal system'

To be savvy consumers, people should be aware how easily marketers can exploit our preferences for round numbers to heighten our sense of achievement, Gunasti said.

"Don't be a slave to the decimal system," he said. "Numbers are symbolic representations that can be easily manipulated."

Someone who can do 19 pushups should feel a similar sense of accomplishment to performing 20 pushups, he said.

And if a weight loss program tells you you've lost 300 ounces?

"Run the numbers," Gunasti said. "Congratulations: You've lost 18.8 pounds."

Archaeologists from the University of Bradford have examined ear ossicles taken from the skeletons of 20 juveniles, excavated from an 18th and 19th century burial ground in Blackburn. They were chosen to represent those with and without dietary disease such as rickets and scurvy.

These children, who were excavated by Headland Archaeology, were examined at the University by Masters student Tamara Leskovar, under the supervision of Dr Julia Beaumont.

The new method has provided a link between the maternal pre-pregnancy diet and the late pregnancy diet found in the earliest tooth tissue. In particular it provides information on the health of the mother and baby in the first two trimesters of pregnancy.

Building on Dr Beaumont's previous research using teeth, the team identified that a person's ossicles can provide a correlation between diet and physiology, with the potential to identify children at risk of disease in later life and to study maternal and infant health in ancient populations.

Dr Beaumont said: "Our previous research has shown that teeth can tell us a lot more than people think. What we didn't realise is just how much one of the smallest bones in the body, our ear ossicle, can also tell us.

"It is formed early on, when the child is in the womb and finishes developing in the first two years. Unlike other bones, it then doesn't remodel, therefore providing a unique snapshot of the health of the mother during the early stages of pregnancy."

"This is the first time human ear bones have been used to investigate diet in the womb. This will allow us, in combination with the dentine, to work out the health of childbearing women who because of the slow rate of bone turnover have been invisible to us."

A study of the world's oldest, continuously-studied birth cohort tracked blood pressure from early adulthood through to late life and explored its influence on brain pathologies detected using brain scanning in their early 70s.

Ages 36-53 appear to be a 'sensitive period' when high blood pressure and large increases in blood pressure might be particularly damaging to the brain.

Authors suggest that for optimising brain health, routine blood pressure monitoring may need to start at, or even before, the age of 40 years - the age when the NHS health check is first offered.

High blood pressure and large increases in blood pressure in midlife may be associated with brain pathologies in later life, according to an observational study of 502 people who have been tracked since their birth in 1946, published in The Lancet Neurology journal.

The study suggests that high blood pressure (140/90 mm Hg or higher) may lead to reductions in brain volume and higher levels of white matter hyperintensities within the brain (white matter brain lesions), but not with reduced cognition or the build-up of beta-amyloid plaques - one of the key proteins associated with Alzheimer's disease.

High blood pressure is known to increase risk for cognitive impairment later in life, but exactly how and when it increases risk is unclear. The new study tracked blood pressure from ages 36-69 to explore its influence on the brain, and found that the link may be there from a younger age than anticipated. The authors suggest that blood pressure monitoring and interventions may need to start at, or before, 40 years to maximise later brain health.

Lead author Professor Jonathan M Schott, University College London, UK, says: "Our research builds on existing evidence around the role of blood pressure and subsequent brain pathology. We found that higher and rising blood pressure between the ages of 36 and 53 had the strongest associations with smaller brain volume and increases in white matter brain lesions in later life. We speculate that these changes may, over time, result in a decline in brain function for example impairments in thinking and behaviour, so making the case for targeting blood pressure in mid-life, if not earlier" [1]

502 participants from the Insight 46 birth cohort (born in Britain in one week in 1946) who were cognitively healthy at the age of 70 were enrolled in the study. All participants had had blood pressure taken at 36, 43, 53, 60-64, and 69 years old, and blood pressure changes between the readings were calculated.

The researchers measured each participant's overall brain volume at about 70 years of age, along with the volume of the hippocampus, the extent of white matter brain lesions, amount of beta-amyloid plaques, and cognitive capabilities.

In the cognitively normal individuals, the researchers found that having higher blood pressure at age 53 and greater increases in blood pressure between 43 and 53 were associated with having more white matter lesions at 70 (e.g. having 10mmHg higher systolic or diastolic blood pressure when aged between 43 and 53 was associated with about 7% and 15% more white matter lesions, respectively). Higher blood pressure aged 43 and greater increases in blood pressure from the age of 36 were associated with having smaller brain volumes (e.g. having a 10mmHg higher diastolic blood pressure aged 43 was associated with having a 6.9mL smaller brain at about age 70).

There was however no evidence that blood pressure affected cognition or the build-up of beta-amyloid plaques. This suggests that associations between midlife blood pressure and late-life brain health are unlikely to be occurring through the build-up of beta-amyloid, which is thought to be one of the earliest changes seen in Alzheimer's disease.

The study suggests that the fourth to sixth decades of life could be a sensitive phase when higher blood pressure and increases in blood pressure have particular impact on the future health of the brain. The authors believe that routine blood pressure measurement may need to start at, or before, 40 years old, and that different approaches to blood pressure change may be needed at different ages.

Co-author, Dr Josephine Barnes, University College London, UK, says: "Our study design provides a unique opportunity to examine blood pressure at different ages, blood pressure changes during specific periods from early adulthood to late life, and to explore their influences on brain pathologies and brain volumes. As increases in blood pressure and higher blood pressure between the ages of 36 and 53 seem to have a detrimental effect on brain health in later life, these findings reinforce the need for monitoring blood pressure even before mid-life." [1]

The authors highlight several limitations. As with any birth cohort, participants have gone through life phases at the same time, and will have been exposed to the same treatments and targets for blood pressure which may differ from people of different ages, meaning the results may be less generalisable to people in other age groups. The Insight 46 cohort is exclusively white British people, and additionally slightly underrepresents people with poor overall health, which reduces how these findings can be applied to different populations. The individuals included in the analyses were cognitively normal, and, as only few individuals in their early 70s have cognitive decline, the authors believe that the cognitive effects of the brain changes they observed may be seen later in life. And finally, there are other brain pathologies which can lead to dementia which further research should explore.

In a linked Comment, Dr Lenore J Launer of the National Institute on Ageing, NIH, Bethesda, USA, states: "Although there are several major translational efforts to more completely understand the complexity of blood pressure-cognitive-related outcomes, the simple association between blood pressure and cognitive-related brain pathology is unlikely to be a chance finding. Millions of individuals have unhealthy blood pressure. Immediate attention should be given to efforts to control blood pressure through clinical services and public health interventions, and to alleviate the barriers to delivery and uptake of these messages."

Changes in blood pressure in those as young as 36 are linked to markers of poorer brain health in later life, finds UCL-led research involving participants of Britain's oldest running birth cohort study.

The findings from the Insight 46 study are published in The Lancet Neurology.

Insight 46 is a neuroscience sub-study of the MRC National Survey of Health and Development (NSHD), the longest running birth cohort in the UK. Insight 46 is designed to follow over 500 birth cohort members to look for early signs and risk factors for dementia as they reach their 70s.

The study, funded by Alzheimer's Research UK, MRC Dementias Platform UK, Wellcome, Brain Research UK, the Wolfson Foundation and the Weston Brain Institute, allows for a unique perspective on the risk factors throughout life that impact brain health at the age of 70.

Blood pressure in midlife has previously been linked to a higher risk of dementia but the mechanism by which this happens, and the time when blood pressure is most important, remain to be fully understood.

To answer these questions, the research team followed 502 individuals from the NSHD, who were all born in the same week in 1946. The participants were free from dementia at the start of the study and 465 underwent brain scans to assess their brain health. Due to the nature of the birth cohort, the researchers were able to measure their blood pressure at 36, 43, 53, 60-64 and 69 years.

The brain scans looked for levels of a key Alzheimer's protein, amyloid, in the brain. The scans also assessed the size of the brain - an indicator of brain health - and the presence of blood vessel damage in the brain.

The results showed that higher blood pressure at the age of 53 and faster rises in blood pressure between 43 and 53 were associated with more signs of blood vessel damage or 'mini strokes' in the brain when an individual was in their early 70s.

Higher blood pressure at the age of 43 and greater increases in blood pressure between the ages of 36 and 43 were associated with smaller brain volumes.

Blood pressure was not associated with the amount of amyloid protein in the brain and did not appear to predict memory and thinking problems at this age.

Professor Jonathan Schott (UCL Queen Square Institute of Neurology), said:

"This unique group of individuals, who have contributed to research their entire lives, has already shaped our understanding of the factors influencing health throughout life. The Insight 46 study has allowed us to reveal more about the complex relationship between blood pressure and brain health. The findings suggest that blood pressure even in our 30s could have a knock-on effect on brain health four decades later.

"We now know that damage caused by high blood pressure is unlikely to be driven through the hallmark Alzheimer's protein amyloid, but through changes in blood vessels and the brain's architecture. The findings show that blood pressure monitoring and interventions aimed at maximising brain health later in life need to be targeted at least by early midlife."

Dr Carol Routledge, Director of Research at Alzheimer's Research UK, said:

"Although this study must continue to assess the impact of blood pressure on dementia risk, the findings shed new light on the mechanism by which hypertension could damage the brain. As the participants in this study are identical ages and have been followed throughout life, the researchers can gain robust insights into the factors influencing their brain health.

"High blood pressure in midlife is one of the strongest lifestyle risk factors for dementia, and one that is in our control to easily monitor and manage. Research is already suggesting that more aggressive treatment of high blood pressure in recent years could be improving the brain health of today's older generations. We must continue to build on this insight by detecting and managing high blood pressure even for those in early midlife."

The Insight 46 study will continue to monitor these participants in the years to come to explore whether those with worse brain health are more prone to cognitive decline and dementia.

Pollution of lakes is a worldwide problem. Restoration attempts take a lot of time and effort, and even then they might backfire. A team of researchers led by the Netherlands Institute of Ecology (NIOO-KNAW) suggests a different approach. First, you have to determine to which of four different types your lake belongs, they write in the August issue of Science of the Total Environment. Spatial differences are the key to a successful restoration recipe.

"Not all lakes are alike", says researcher and first author Annette Janssen. Even if the problem is the same: pollution, usually caused by too many nutrients. Instead of making a lake healthier, an oversupply of phosphorus or nitrogen will turn the water into 'green soup' - which is toxic, too, in many cases. "For an effective solution, you have to take into account the spatial differences between lakes." It's a factor that, until now, had been largely neglected.

Where and how do nutrients enter the lake? And where does the water originate? There are lakes with a single point of entry - e.g. a pipeline or a river feeding the lake - and lakes where the nutrients and/or the water enter in a more diffuse way: from groundwater or precipitation. Based on these spatial differences, the researchers distinguish between four types of lakes, all of which would require a different restoration approach.

Type 'Loosdrecht'

Take Lake Loosdrecht in the Netherlands. Its natural situation is for nutrients and phytoplankton to be relatively homogeneously distributed. It's a seepage lake, which means the water, too, enters in a relatively diffuse way. In lakes of this type, says Janssen, flushing with clean water often proves to be successful.

A lake that belongs to an entirely different category is Lake Taihu near the Chinese city of Shanghai, where Janssen did much of her PhD research. Lake Taihu is fed by a river, and close to its mouth a thick layer of smelly algae covers the water. At the outflow, on the other hand, the water is relatively clean. An attempt by the authorities to flush this lake did not work out well. Janssen: "In lakes of the Type 'Taihu', flushing only spreads pollution across a larger area, like an oil spill." The same is true for lakes of the Type 'Pátzcuaro' (Mexico), which are point-loaded seepage lakes.

In lakes of the Type 'Tahoe' (United States), finally, flushing does work, as the highest concentration of nutrients is found at the outflow and would therefore leave the lake quite rapidly. But another promising approach - the removal of certain species of fish (bio-manipulation) - only seems to work in lakes of the same type as Lake Loosdrecht. There, it will help to give plants and animals linked to having clear water the space they need.

Reducing nutrients

"But the only thing that can lead to a permanent recovery in all four lake types", conclude the NIOO-researchers and their colleagues from Wageningen UR, PBL Netherlands Environmental Assessment Agency, Witteveen+Bos and the United States Geological Survey, is "to reduce the supply of nutrients." That's tricky, to say the least. But thanks to a recent Veni grant from the Dutch Research Council, Annette Janssen will be getting down to work on this soon.

A new study led by University of Chicago researchers suggests a significant link between exposure to environmental pollution and an increase in the prevalence of neuropsychiatric disorders.

Based on analysis of large population data sets from both the United States and Denmark, the study, published in PLoS Biology, found poor air quality associated with increased rates of bipolar disorder and major depression in both countries.

"Our studies in the United States and Denmark show that living in polluted areas, especially early in life, is predictive of mental disorders," said computational biologist Atif Khan, PhD, the first author of the new study. "These neurological and psychiatric diseases--so costly in both financial and social terms--appear linked to the physical environment, particularly air quality."

Khan and Andrey Rzhetsky, PhD, Edna K. Papazian Professor of Medicine and Human Genetics and the paper's senior author, used a U.S. health insurance database of 151 million individuals with 11 years of inpatient and outpatient claims for neuropsychiatric diseases. They compared the geo-incidence of claims to measurements of 87 potential air pollutants from the United States Environmental Protection Agency (EPA). The counties with the worst air quality had a 27 percent increase in bipolar disorder and 6 percent increase in major depression when compared to those with the best air quality. The team also found a strong association between polluted soil and an increased risk of personality disorder.

Because these correlations seemed unusually strong, the team sought to validate their findings by applying the methodology on data from another country. Denmark tracks environmental quality indicators over much smaller areas (a little over one-quarter of a mile) than does the EPA. The UChicago team collaborated with Denmark-based researchers Aarhus to analyze Danish national treatment registers with data from 1.4 million people born in Denmark between 1979 and 2002. The researchers examined the incidence of neuropsychiatric disease in Danish adults who had lived in areas with poor environmental quality up to their tenth birthdays.

The associations the team found, especially for bipolar disorder, mirrored those in the United States: a 29 percent increase for those in counties with the worst air quality. Using this more specific Danish data, the team found early childhood exposures correlated even more strongly with major depression (a 50 percent increase); with schizophrenia (a 148 percent increase); and with personality disorders (a 162 percent increase) over individuals who grew up in areas with the highest quality air.

Researchers have long suspected that genetic and neurochemical factors interact at different levels to affect the onset, severity and progression of these illnesses. So far, scientists have found only modest associations between individual genetic variants and neuropsychiatric disease: for most common polymorphisms, disease risk increase is small, perhaps less than 10 percent. This fact led Rzhetsky, who has been studying the genetic roots of a wide variety of neuropsychiatric diseases for over two decades, to look for other molecular factors that might trigger or contribute to the disease mechanism.

Khan, Rzhetsky and the team worked on the project for over two years, enhancing their models with additional mathematical analyses and data sources. Nevertheless, their findings are not without controversy: other researchers in the field have noted that this substantial correlation still does not confirm pollution actually triggers the diseases. Rzhetsky's previous work on the correlation between air quality and asthma - which used similar methodology - met with no resistance from journals or the broader scientific community. Rzhetsky adds that in experiments on animals exposed to pollution, the animals show signs of cognitive impairment and depression-like behavioral symptoms.

While the study did not address the question of how air pollution might trigger neural effects, a large body of experimental studies in animal models suggests that polluting chemicals affect neuroinflammatory pathways and set the stage for later neurodevelopmental problems--many of which occur at the end of childhood as children become adults.

It turns out that British food isn't that terrible, after all. A global survey has found that when it comes to having the healthiest packaged foods and drinks, the UK tops the charts, with the USA in 2nd place and Australia coming in at 3rd.

The George Institute for Global Health analysed more than 400,000 food and drink products from 12 countries and territories around the world. The survey highlights the high levels of sugar, saturated fat, salt and calories/kJ in many of our favourite food items.

The countries were ranked using Australia's Health Star Rating system - which measures the levels of the nutrients such as energy, salt, sugar, saturated fat as well as protein, calcium and fibre and assigns a star rating from ½ (least healthy) to 5 (the most healthy).

It found that the UK had the highest average Health Star Rating of 2.83, followed by the US at 2.82 and Australia at 2.81. India got the lowest rating of just 2.27 followed by China at 2.43 with Chile coming third from bottom at 2.44. The results were published in Obesity Reviews.

Lead author Dr Elizabeth Dunford said the results were concerning because packaged foods and drinks are driving a double burden of diet-related diseases in many low- and middle-income countries.

"Globally we're all eating more and more processed foods and that's a concern because our supermarkets shelves are full of products that are high in bad fats, sugar and salt and are potentially making us sick. Our results show that some countries are doing a much better job than others. Unfortunately it's the poorer nations that are least able to address the adverse health consequences that have the unhealthiest foods."

Key results

China's drinks were some of the healthiest in the survey with an average Health Star Rating of 2.9 but packaged foods scored low at just 2.39.

South Africa on the other hand scored low with its drinks at an average 1.92 Health Star Rating whilst its foods came in at 2.87.

Canada topped the list for unhealthy salt levels in foods and drinks with an average of 291mg/100g of sodium, with the US coming in 2nd at 279mg/100g.

The UK scored best for sugar at just 3.8 grams per 100 g with Canada second best at 4.6 grams per 100 g.

China's packaged foods and beverages had the most harmful levels of saturated fat. They also scored worst for average sugar levels at 8.5 grams per 100 g (more than 2x the UK's average) - with India in 2nd place at 7.3 grams per 100 g.

India's packaged foods and drinks were most energy dense (kilojoule content 1515 kJ/100 g) and South African products were least energy dense at an average of just 1044kJ/100 g.

Co-author Professor Bruce Neal, Acting Executive Director of The George Institute, Australia said with packaged foods progressively dominating the world's food supply there was real cause for concern.

"Billions of people are now exposed to very unhealthy foods on a daily basis. The obesity crisis is just the first ripple of a tsunami of dietary ill health that is coming for us. We have to find a way that the food industry can profit from selling rational quantities of quality food, rather than deluging us with unhealthy junk. There are few greater priorities for human health.''

The report notes that many of the world's major food and drink manufacturers have signed up to the International Food and Beverage Alliance and made pledges to reduce levels of salt, sugar and harmful fat and that these findings could provide an impetus for companies to improve the healthiness of their product ranges.

The lab of Cheryl Kerfeld at Michigan State University has created a synthetic nano-sized factory, based on natural ones found in bacteria. This research could someday lead to new medical, industrial or bioenergy applications.

The new study is published in Metabolic Engineering.

Natural nanofactories are found in bacteria all over the planet. Some make nutrients. Others sequester toxic materials that would otherwise make the bacteria sick -- or even die.

But all factories share a common exterior, a shell made of protein tiles. Scientists want to design new factories, based on those found in bacteria naturally, for use in biotechnology.

One way to direct useful enzymes to these factories is by physically attaching them to the tail ends of the proteins that make up the factory shells. But there is a catch.

The ends, or termini, of most shell proteintiles face the outside of a factory. So any molecules fused to the protein ends will end up on the outside surface and not the inside. This is a problem if the goal is to keep one or more enzymes inside a factory separated from the rest of the cell.

"In order to send proteins to the inside of the factory, we needed a new kind of building block that still assembled into shells," said Bryan Ferlez, a post doctorate researcher in the Kerfeld lab. "We aimed to redesign a shell protein so its termini face the inside. The end result is that cargo connected to this shell protein would also end up inside the shell."

In the new study, the scientists take the most abundant shell protein, called BMC-H, and turn it 'inside-out' through a technique called circular permutation.

They shuffle segments of the the amino acid sequence and glue the original ends together. They then introduce new termini on the inner face of the protein. The result is a new, synthetic shell protein that looks almost identical to its natural counterpart. Except now, both new ends face the inside of the shell.

The new structure is a usable building block to construct factory shells.The scientists have successfully produced factory shells, with the new protein. They are similar in size and appearance to the original shells.

The new structure can incorporate molecules inside the shell. The team tested the concept by fusing a fluorescent cargo protein to the new BMC-H protein. Microscopy and biochemical testing show the cargo on the inside of the shell.

Scientists can control the amount of cargo imported into the new structure.

"By making more or less of the new BMC-H protein with a fluorescent protein fused to its terminus, we were also able to control the amount of cargo that incorporates into the shell," Ferlez said.

Next, Ferlez wants to target 'useful' molecules into a synthetic factory made with the new shell protein.

"We can start to build metabolic pathways, or assembly lines, and define the amounts and locations of enzymes within these nanofactories. Someday, we could use this system to enhance the production of rubber, biofuels, and other commodities," Ferlez explained.

LOS ANGELES - Better access to on-demand transportation could help older adults miss fewer medical appointments as well as reduce their social isolation to improve their overall health, suggests a new study published in the Journal of mHealth by researchers at the USC Center for Body Computing (USC CBC) at the Keck School of Medicine of USC.

USC CBC researchers provided free and unlimited Lyft rides for three months to 150 older patients with chronic disease to see if better access to transportation could improve their access to medical centers and reduce their social isolation. The researchers also wanted to know its overall impact on their health.

Ninety-three percent of patients used the Lyft rides to access medical care and a significant number learned to use smartphone apps and a telephone concierge service to do so. While visiting their doctors counted for a third of all rides (31%), the seniors used the remaining rides to get to fitness, social and leisure activities, and reported that this improved their perceived quality-of-daily-life (92%).

"Access to transportation is more than getting from point A to point B; it encompasses multiple human facets of life," says Leslie Saxon, MD, executive director of the USC Center for Body Computing and principal investigator of the study. "This research underscores how ride-sharing platforms can provide a significant benefit to the well-being of older adults, empowering them to become active participants in their own care as well as in other areas of their lives."

The researchers concluded that while older adults can be willing, even enthusiastic novel technology adopters who are motivated to overcome barriers disrupting their own health, they needed education and support to be successful.

In the study, 150 English-speaking Keck Medicine of USC patients over the age of 60 (63% female and 54% Caucasian) with chronic diseases were screened for psychological factors and to ensure that access to transportation was a factor in missed appointments. The patients lived an average of 20 miles away from Keck Medical Center of USC and over 45% relied on others for transportation.

The patients were offered free rides to both medical and non-medical destinations for three months and received personalized training in summoning a ride from a ride-sharing app. They also had the option to schedule rides via the Lyft phone concierge platform. Each participant was assigned a wrist-worn daily activity tracker.

The majority of older adults reported that cost was the primary barrier preventing them from continuing to use the ride shares after the study concluded, as the average cost of a month of unlimited rides in Los Angeles is $500. "Because study participants expressed challenges with the costs associated with ride-sharing, our next steps will be to compare the long-term costs of using these apps for health care needs versus the opportunity costs of inconsistent access to transportation," Saxon says. "Our findings on the benefits to seniors could incentivize similar programs on a larger scale by cities and insurance companies."

The study was supported by a $1 million grant from the AARP Foundation as part of a broader collaboration with UnitedHealthcare to address the needs of seniors. Lyft provided the rides and transportation data as well as the app and telephone concierge platform.

"Access to reliable, affordable transportation is essential for older adults," says Lisa Marsh Ryerson, president of AARP Foundation. "When older adults can't get to medical appointments or social activities, the negative effect on well-being -- whether from untreated medical conditions or lack of social interaction -- is enormous. This study highlights the vital connection between good transportation and good health in our communities, especially for seniors who can no longer drive."

In the confines of the thoracic chamber, a heart has lost its rhythm. Its two upper chambers, the atria, are beating out of sync with the two lower chambers, the ventricles. The resulting chaos is called atrial fibrillation and is a major concern because it prevents the heart from pumping effectively and is associated with serious complications including heart failure, dementia and a fivefold increase in the risk of stroke.

The laboratories of Dr. Xander Wehrens at Baylor College of Medicine and Dr. Stephan Lehnart at the University of Goettingen in Germany are making headway into understanding the molecular mechanisms that underlie this devastating rhythm disorder.

What is at the 'heart' of a heartbeat?

"At the molecular level, calcium is essential for maintaining a healthy heartbeat," said Wehrens, professor of molecular physiology and biophysics and the Juanita P. Quigley Endowed Chair in Cardiology at Baylor. "Proper contraction and relaxation of the heart depends on the coordinated flux of calcium ions in and out of individual cardiac muscle cells. Research in our lab focuses on understanding how these calcium dynamics are regulated in normal and diseased hearts."

Cardiac cells store calcium in a specialized compartment called the sarcoplasmic reticulum, or SR. "Upon electrical activation of the cell, calcium released from these SR compartments binds to the contractile system and causes contraction," said first author Dr. Katherina M. Alsina, who was a graduate student during the development of this project and is currently senior project manager in the Cardiovascular Research Institute. "Then, the same calcium that was released has to be channeled back into the SR so the cell can relax."

It has been well established that the activities of the SR calcium release and reuptake systems are altered in cells from patients with atrial fibrillation, and that the resulting defects in calcium cycling contribute to the pathogenesis of the disease. Until now though, these two processes, (SR calcium release and reuptake), were thought to be mediated by different and separate systems, but the work from Wehrens and colleagues is changing that model.

Lehnart, professor of cardiology and pulmonology and co-corresponding author of this study, explains that the group's findings shift the long-standing paradigm that SR calcium release and reuptake complexes are separate and discrete functional entities. "Assemblies of multiple proteins, also called protein complexes, are at the center of cardiac function, regulation and disease. Using an unbiased strategy for analysis, we identified a super-complex of two essential protein machines, a calcium release channel and a calcium reuptake pump, and found that both are actually regulated by the same molecular mechanism in heart cells."

A new piece of the puzzle

As Wehrens, Alsina, Lehnart and their colleagues explored the molecular players involved in regulating SR calcium cycling, they discovered a new piece of the puzzle that has changed the field's understanding of the molecular mechanisms leading to atrial fibrillation.

Using an unbiased technique called complexome profiling, Wehrens and colleagues found that a phosphatase regulatory subunit known as PPP1R3A binds to both the SR calcium release and reuptake complexes, forming one big super-complex that is present in atrial cells from both mice and humans. Furthermore, using a new imaging technique called 'STimulated Emission Depletion' (STED) super-resolution microscopy, the team visually confirmed that these two complexes are very close to each other.

"With traditional confocal microscopy we see blurry spots, but with STED we can clearly see individual molecules and estimate the distance between them," said Wehrens, who is the director of the Cardiovascular Research Institute. "We found that components of the calcium release complex overlap with components of the calcium reuptake complex, and that this super-complex is also present in tissue samples from human atria."

PPP1R3A seems to be at least one of the molecular regulators involved in maintaining the integrity of this newly identified calcium-handling super-complex. Genetic deletion of PPP1R3A in mice disrupted the formation of the super-complex, promoted abnormal SR calcium cycling and increased susceptibility to atrial fibrillation.

In addition, the researchers found that levels of PPP1R3A were decreased and the super-complex disrupted in atria of human patients with atrial fibrillation. These findings may have exciting implications for the future of atrial fibrillation treatments. As Wehrens explained, "a reduction in the amount of PPP1R3A may explain two defects in calcium handling in atrial fibrillation, opening the possibility of treating both defects at the same time."

Lehnart emphasized that these findings were only possible through the combined efforts of multiple labs across the world. "Our joint work, which originated through independent efforts and methodologies in different laboratories, also shows the importance of international collaboration to understand and eventually develop new therapies for complex diseases such as atrial fibrillation."

A new rechargeable high voltage manganese dioxide zinc battery, exceeding the 2 V barrier in aqueous zinc chemistry, is the latest invention by City College of New York researchers. With a voltage of 2.45-2.8V, the alkaline MnO2|Zn battery, developed by Dr. Gautam G. Yadav and his group in the CCNY-based CUNY Energy Institute, could break the long dominance of flammable and expensive lithium (Li)-ion batteries in the market.

To break the previously daunting 2 V barrier in aqueous zinc chemistry, primary inventor Yadav and his team interfacially engineered two different aqueous electrolytes that deliver the theoretical capacity (308mAh/g) reversibly for many cycles.

"The voltage of current commercially available alkaline MnO2|Zn batteries is around 1.2-1.3V, and this has been considered low compared to Li-ion which has a voltage >3V," said Yadav.

Voltage has been Li-ion's greatest asset and has helped fuel its rise in an energy hungry world.

"Unfortunately it contains elements that are toxic and geopolitically sensitive with Asian countries having a monopoly on mining and manufacturing them," added Yadav.

"This has put the United States at a tremendous disadvantage and has lost its lead in energy storage industry, when in the past it was a world leader. With Mn and Zn being widely available elements, and with the U.S. being rich with them as well, it allows the U.S. to compete again. The manufacturing cost of these batteries will also be low, so it can kick start the growth of the energy storage industry in the U.S."