Culture

Mutation links bipolar disorder to mitochondrial disease

image: This is an abstract rendition of the paper's themes.
Mutations in the gene ANT1 may confer a risk for bipolar disorder through a complex interplay between serotonin and mitochondrial signaling in the brain.

Image: 
Milena Menezes Carvalho/RIKEN National Science Institute

Mutations in the gene ANT1 may confer a risk for bipolar disorder through a complex interplay between serotonin and mitochondrial signaling in the brain. These two pathways have been separately implicated in bipolar disorder, but the link between levels of the neurotransmitter serotonin and mitochondrial dysfunction had not been established. Researchers at the RIKEN Center for Brain Science (CBS) in Japan now report that mitochondrial dysfunction affects the activity of serotonergic neurons in mice with mutations of ANT1.

Mitochondria are the vital organelles that deliver energy to all cells and mitochondrial damage has been found, for example, in brain imaging of bipolar patients and in post-mortem brains. Roughly 20% of patients with mitochondrial disease also have bipolar disorder, a major psychiatric disease characterized by manic and depressive episodes. Altered serotonin functioning, on the other hand, seems to be involved in bipolar disorder because drugs that target serotonin levels can effectively treat the condition. "Our study suggests that mitochondrial dysfunction can alter activity of serotonergic neurons in bipolar disorder, and this is the first time these two lines of evidence have been linked," says Tadafumi Kato, research group leader at CBS. The research was published on June 8 in the journal Molecular Psychiatry.

The study started by identifying ANT1 mutations in patients with bipolar disorder. Kato and colleagues then looked at mice lacking the ANT1 gene in the brain only. Compared with non-mutant mice, the mitochondria in these knockout mice could not retain calcium and had leakier pores. The ANT1-mutant mice also showed lower impulsivity in behavior tests, and consistent with this, their brains showed elevated serotonin turnover. This hyper-serotonergic state is likely a result of a cascade of changes that starts with the loss of the ANT1 gene and the resulting dysfunctional mitochondria. Enhanced serotonergic activity may then further impair mitochondria in a vicious cycle.

Serotonergic neurons were found to deteriorate in a brain area called the dorsal raphe, which is a region also affected in Parkinson's disease--another condition that may have its roots in mitochondrial dysfunction. The ANT1 mutation does not cause bipolar disorder, says Kato, but is associated with elevated risk. The implication of this research is that emerging therapies for the underlying mitochondrial dysfunction could one day treat bipolar disorder more successfully than today's variable serotonin-targeting drugs.

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RIKEN

Reporting and evaluating wait times for urgent hip fracture surgery in Ontario, Canada

About two-thirds of patients admitted to hospital in Ontario for hip fracture did not receive surgery during the recommended time window of 24 hours, according to a new study in CMAJ (Canadian Medical Association Journal )http://www.cmaj.ca/lookup/doi/10.1503/cmaj.170830.

Hip fracture is the most common reason for urgent surgery in Canada, and numbers are increasing, with more than 30 000 procedures performed annually.

"We found whether patients receive surgery on time is arbitrary, and mostly depends on which hospital they are taken to, indicating that efforts to improve wait times in Ontario should focus on improving performance at the hospital level," says Dr. Daniel Pincus, Institute for Clinical Evaluative Sciences, Toronto, Ontario.

The study includes data on 42 230 patients aged 45 years or older who had hip fracture surgery between April 2009 and March 2014. They were treated by 522 surgeons and 963 anesthesiologists from 72 hospitals across Ontario, Canada's largest province. The mean age was 80 years and most patients were female.

"Wait times varied significantly depending on where patients were treated, with more than half of hospitals (51%) showing significant difference in the likelihood of delayed surgery for hip fracture that was not attributable to patient or physician factors," write the authors.

Factors that led to delayed surgery include transferring patients to another hospital for surgery, preoperative consultations from internal medicine and anesthesia, and performing echocardiograms.

"Wait time initiatives have previously focused on the time spent waiting for specialist consultation, elective surgery and assessment in the emergency department," adds Pincus. "Canadians may be surprised to learn that wait times in our system also exist for patients requiring urgent and emergency procedures, now that accurate wait times can be measured for these types of procedures using techniques from the paper."

The authors make several suggestions to improve wait times, including performing elective surgeries later in the day and introducing policies to address delays around patient transfer from smaller hospitals.

"Policy that guarantees elective cases would be completed later in the day, even if non-elective cases are prioritized before them, may improve wait times for urgent procedures without the need to increase capacity in operating rooms," write the authors.

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Canadian Medical Association Journal

Moderate and extreme temperatures could increase the risk of occupational injuries

Moderate and extreme ambient temperatures increase the risk of occupational accidents. This is the main conclusion of a new study by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Banking Foundation. The study analysed data on nearly 16 million occupational injuries that occurred in Spain over a 20-year period.

Heat and cold are believed to be associated with a higher risk of occupational injury, but the existing scientific evidence consists of only a handful of studies with a small number of cases and a limited geographic scope, and the economic impact has never been analysed in detail.

The new study, published in Environmental Health Perspectives, is the first to analyse data from an entire country and evaluate the economic impact. Researchers analysed data related to nearly 16 million occupational injuries in Spain between 1994 and 2013 that resulted in at least one day of sick leave. This information was analysed in relation to the daily temperatures in the province where each injury occurred.

"Exposure to moderate to extreme temperatures may have played a role in over half a million of the workplace injuries that occurred during the study period," commented ISGlobal researcher Èrica Martínez, lead author of the study. The analysis found that, on average, some 60 temperature-related injuries leading to at least one lost workday occurred each day, accounting for 2.7% of all work-related injuries in Spain. Extremes of cold and heat increased the risk of injury by 4% and 9%, respectively.

The biological mechanisms that link exposure to extreme ambient temperatures with the risk of occupational injury "are not yet fully understood", explained Martínez. The most common types of injuries analysed in the study were bone fractures and superficial injuries. "This suggests that the underlying mechanism could be related to impaired concentration or judgement, which would affect occupational safety," noted the researcher. Moreover, temperature-related effects were not limited to the day of exposure; a "pattern of delayed impact", possibly caused by cumulative fatigue and dehydration, was observed in the days following exposure.

The study also concluded that women appear to be more vulnerable to cold and men more vulnerable to heat. This difference could be explained by the fact that women have lower sweat rates than men in hot climates. The youngest workers were the most vulnerable to heat, possibly because they tend to do more physically demanding work.

As for the economic impact of nonoptimal temperatures, the study found that temperature-related loss of working days had an annual cost of more than €360 million, representing 0.03% of Spain's gross domestic product in 2015. Moderately high temperatures contributed the most to the economic losses.

"In the present context of climate change, these results indicate that public health interventions are needed to protect workers," concluded ISGlobal researcher Xavier Basagaña, the study coordinator. "Most workplace injuries can be attributed to moderate heat and moderate cold. This shows us how important it is for public health policies and plans to take moderate temperature ranges into account, since they are more common than extreme temperatures and account for a larger share of total injuries."

Preventive measures that could be incorporated into public health policies include restricting work during the coldest and hottest hours, taking rest breaks, ensuring proper hydration and wearing appropriate work clothes.

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Barcelona Institute for Global Health (ISGlobal)

Enzyme found to control formation of collagen carriers and inhibit collagen secretion

image: Electron microscopy imaging reveals the presence of many interconnected vesicles, which appear to behave like collagen carriers (indicated by arrows).

Image: 
<i>Biochemical and Biophysical Research Communications</i>

Researchers at Tokyo Institute of Technology (Tokyo Tech) have identified an enzyme that controls how much our cells secrete collagen. As collagen imbalance is linked to a range of human diseases, the study provides clues to new therapeutic strategies. Moreover, the findings could facilitate efficient production of collagen for the food, cosmetic and pharmaceutical industries.

All of our cells make and release proteins. The proteins are packaged as "cargo" in tiny, bubble-like vesicles before being transported outside the cell. This process, known as secretion, is vital to healthy growth and development.

Although many studies have shown how these vesicles, called COPII carriers[1], handle relatively small-sized cargo, few have focused on the workings of unusually large carriers known to package very large proteins, such as collagen.

Now, a study by researchers including Masayuki Komada, Toshiaki Fukushima and graduate student Kohei Kawaguchi at Tokyo Institute of Technology has identified USP8 as a key enzyme involved in controlling the formation of large collagen carriers. They have reported their findings in the journal Biochemical and Biophysical Research Communications.

The team showed that "switching on" USP8 inhibited the formation of large carriers, and thus reduced collagen secretion. Conversely, switching USP8 off promoted collagen transport, which led to increased collagen secretion. (See Figures 1-3.)

The findings have big implications for medicine and biotechnology. Excessive collagen secretion in the human body is known to cause organ fibrosis[2], while too little collagen secretion is associated with bone diseases including cranio-lenticulo-sutural dysplasia (CLSD) and Cole-Carpenter syndrome. New treatments for these diseases could be developed through further understanding of USP8's exact mode of action. Such knowledge could also provide new ways of scaling up commercial production of collagen.

The researchers have demonstrated that the enzyme works by deubiquitinating a protein called Sec31A, a component of the COPII vesicle coat required for protein export.

One particular group of proteins called the USP8-STAM1 complex[3] appears to be responsible for deubiquitinating Sec31A, as illustrated in Figure 3.

The study builds on many years of research that have illuminated the versatility of USP8.

"We had previously reported that USP8 regulates pituitary hormone secretion[4]," says Fukushima, referring to a paper published in Nature Genetics in 2015. "In the process of that study, we accidentally found that the USP8-STAM1 complex binds to Sec31."

It was this "accidental" finding, combined with promising results from other groups in the US, that led the team to examine the role of USP8 in the formation of COPII carriers.

In research tracing back more than a decade, Komada and others have clarified the conventional role of USP8 in the regulation of endocytosis5. "It's very interesting that the same USP8-STAM1 complex has now been shown to play an important role both in the regulation of endocytosis and in secretion," Fukushima says.

The present study therefore reveals a "new face" of the USP8 enzyme, and Fukushima hints that there may be more surprises to come. USP8 belongs to a family of around 90 known deubiquitinating enzymes, which continue to be a hot topic in cellular biology.

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Tokyo Institute of Technology

Scientists identify foods that fight disease

Boston (June 10, 2018) - The foods we eat play a significant role in our health. Scientists are discovering how eggs, nuts, dairy products, vegetables and even coffee can help protect against health problems. Nutrition 2018 will feature the latest research into how adding certain foods to our diet might help lower risk for diabetes, cancer, neurodegenerative diseases and other health issues.

Nutrition 2018 is the inaugural flagship meeting of the American Society for Nutrition held June 9-12, 2018 at the Hynes Convention Center in Boston. Contact the media team for abstracts, images and interviews, or to obtain a free press pass to attend the meeting.

Improving diabetes risk factors

Eggs may reduce diabetes risk factors

Findings from a 12-week randomized study of overweight or obese individuals with pre- or type 2 diabetes suggests that eggs may help reduce risk factors associated with diabetes. Participants who ate an egg each day showed greater improvements in fasting blood sugar levels and insulin resistance than those who ate an egg substitute. Furthermore, eating eggs did not significantly change cholesterol levels. Shirin Pourafshar, University of Virginia, will present this research on Sunday, June 10, from 1-3 p.m. in the Hynes Convention Center, Auditorium (poster 102) (abstract).

Daily pecans might lower cardiometabolic risk factors

After four weeks of eating a small handful (about 1.5 ounces) of whole pecans daily, overweight adults age 45 or older who were otherwise healthy showed favorable changes in cardiometabolic risk factors including blood sugar levels, insulin resistance and insulin-producing cell function, compared to when study participants consumed a diet similar in total fat and fiber but without daily pecans. Additional research is required to determine if a small daily portion of pecans would help lower the risk of cardiovascular disease and type 2 diabetes for middle-aged and older adults who are overweight or obese. Diane L. McKay, Friedman School of Nutrition Science and Policy at Tufts University, will present this research on Monday, June 11 from 3-5 p.m. in the Hynes Convention Center, Room 309 (abstract).

Combating cancer and loss of motor function

Homing in on dairy products that lower colorectal cancer risk

Researchers studying 101,677 people, ages 54 to 83 years, found that not all dairy products are equal when it comes to reducing colorectal cancer risk. Study participants who consumed low-fat or fermented dairy products such as yogurt showed the lowest risk for developing colorectal cancer. Yumie Takata, Oregon State University, will present this research on Monday, June 11, from 1-3 p.m. in the Hynes Convention Center, Hall D (poster 831) (abstract).

Vegetables and berries help reduce Parkinsonism risk

As a follow-up to a study that linked a healthy diet with a reduced risk of Parkinsonism (a group of neurological disorders that cause movement problems similar to those seen in Parkinson's disease), researchers followed 706 people for an average of 4.6 years to find out if consuming fruits and vegetables may be specifically associated with lowered risk. Their analysis revealed that eating more vegetables (especially green leafy vegetables) and berries, but not other fruits, may reduce the risk of Parkinsonism and slow its progression in older adults. Puja Agarwal, Rush University Medical Center will present this research on Sunday, June 10, from 8 a.m.-6 p.m. in the Hynes Convention Center, Auditorium (poster 22) (abstract).

Components of edible mushrooms fight inflammation

An analysis of PPEP-1 and PPEP-2 polysaccharides from the edible mushroom Pleurotus eryngii reveals that these complex carbohydrates can inhibit induced inflammatory responses. The new results are the first to demonstrate these anti-inflammatory properties and highlight the potential of PPEP-1 and PPEP-2 as dietary supplements to reduce inflammatory responses. Gaoxing Ma, Nanjing Agricultural University; University of Massachusetts, Amherst; will present this research on Tuesday, June 12, from 11:15-11:30 a.m. in the Hynes Convention Center, Room 309 (abstract).

Coffee could be good for the liver

A study of more than 14,000 people, ages 45 to 64, finds that people who drink three or more cups of coffee a day have a lower risk of liver-related hospitalizations than those who never drink coffee. The new findings provide evidence that coffee drinkers may have a lower risk for liver disease. Emily Hu, Johns Hopkins Bloomberg School of Public Health, will present this research on Sunday, June 10, from 1-3 p.m. in the Hynes Convention Center, Auditorium (poster 55) (abstract).

Please note that abstracts presented at Nutrition 2018 were selected by a committee of experts but have not generally undergone a rigorous peer review process such as that required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

Credit: 
American Society for Nutrition

American toddlers consume too much added sugar

A new study suggests children in the US begin consuming added sugar at a very young age and that many toddlers' sugar intake exceeds the maximum amount recommended for adults.

The study found 99 percent of a representative sample of US toddlers age 19-23 months consumed an average of just over 7 teaspoons of added sugar on a given day--more than the amount in a Snicker's® bar. Sixty percent of children were found to consume added sugar before age 1.

Added sugar consumption has been linked with obesity, dental caries, asthma and risk factors for heart disease, such as high cholesterol and high blood pressure. Eating foods with added sugar also can influence a child's food preferences, potentially leading to less healthy food choices later in life, researchers say.

"This is the first time we have looked at added sugar consumption among children less than 2 years old," said lead study author Kirsten Herrick, a nutritional epidemiologist at the Centers for Disease Control and Prevention (CDC). "Our results show that added sugar consumption begins early in life and exceeds current recommendations. These data may be relevant to the upcoming 2020-2025 Dietary Guidelines for Americans."

Herrick will present the research at the American Society for Nutrition annual meeting during Nutrition 2018, held June 9-12, 2018 in Boston.

There is no chemical difference between sugars that are found naturally in fruits, vegetables and milk and sugars that are added to food products during processing or preparation. The body metabolizes natural and added sugars in the same way. However, added sugars are considered more damaging to health because they displace nutritional components of foods and contribute significantly to caloric intake. Foods containing added sugars are often not accompanied by the other nutritional benefits one derives from eating foods that naturally contain sugar, such as the fiber and vitamins contained in an apple.

"The easiest way to reduce added sugars in your own diet and your kids' diet is to choose foods that you know don't have them, like fresh fruits and vegetables," said Herrick.

Herrick analyzed data from more than 800 infants and toddlers between 6-23 months old who participated in the 2011-2014 National Health and Nutrition Examination Survey (NHANES), a research study that is representative of the American population.

Parents were asked to record every item their child consumed during a 24-hour period. To assess added sugar, researchers counted any calorie-containing sugars that were added to a food item, including cane sugar, high-fructose corn syrup, honey and other forms of sugar. The study did not include artificial zero-calorie sweeteners or the sugars that occur naturally in fruits, vegetables and milk.

The results indicate that 85 percent of infants and toddlers consumed added sugar on a given day. Added sugar consumption rose with age. At age 6-11 months, just over 60 percent of babies consumed added sugar on a given day, averaging just under 1 teaspoon. Among those age 12-18 months, 98 percent consumed added sugar, averaging 5.5 teaspoons. By 19-23 months, 99 percent of children consumed an average of just over 7 teaspoons of added sugar on a given day.

The US government's 2015-2020 Dietary Guidelines for Americans (DGA) does not include guidelines specific for children under age 2 although the 2020-2025 edition, soon to be in development, will include dietary recommendations for infants and toddlers. The 2015 DGA Advisory Committee did propose that all Americans cut their intake of solid fats and added sugars as an effective strategy to pare calories and focus more on foods that contribute to a nutrient-rich diet.

Daily recommended limits for added sugar are 6 teaspoons or less per day for children age 2-19 and for adult women and 9 teaspoons or less per day for adult men. Previous research suggests most Americans exceed those limits.

"Once kids start eating table food, they're often eating the same types of foods that Mom and Dad have in their diet, and other research has demonstrated that adults exceed recommendations for added sugar too," said Herrick.

The current study does not indicate which types of food contributed to children's added sugar intake, though the research team plans to examine sources of added sugar in the future. Other studies have identified ready-to-eat cereals, bakery items and other desserts, sugar-sweetened beverages, yogurt and candy to be significant sources of added sugar in children's diets.

Among children aged 12-23 months, Herrick said added sugar consumption was highest among non-Hispanic black children and lowest among non-Hispanic white children. There were no differences in added sugar consumption by race among infants 6-11 months.

The team plans to further investigate the data, including examining trends over time. Other studies have suggested added sugar consumption among American children has declined over the years.

Kirsten Herrick will present this research on Sunday, June 10, from 4:45-5 p.m. in the Hynes Convention Center, Room 306 (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Please note that abstracts presented at Nutrition 2018 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available. Additional resources on infant and toddler nutrition are available from the Centers for Disease Control and Prevention and the Robert Wood Johnson Foundation.

Credit: 
American Society for Nutrition

Drug resistance genes shared among bacteria in hospitals can be deadly

June 10, 2018 - Atlanta, GA - A hospital outbreak of carbapenem-resistant Enterobacteriaceae (CRE) became more worrisome when researchers found resistance genes being shared among unrelated bacteria via plasmids and other mobile genetic elements. This new research will be presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7th through June 11th in Atlanta, Georgia.

In 2017, eighteen patients in a primary care hospital became sick with CRE, a family of bacteria responsible for more than 9,000 healthcare-associated infections (HAI) per year in the United States. Carbapenems are often used as last line treatment options, reserved for the sickest patients; so it is concerning when bacteria resistant to these drugs cause infections.

Outbreaks of CRE infections are often caused by closely related bacteria spreading from person-to-person or even from a common source, such as a contaminated medical device. In such cases, infection control efforts focus on eliminating transmission of a single strain of bacteria. In this outbreak, however, multiple types of CRE (i.e., different bacterial strains and species) were infecting patients, and whole genome sequencing revealed that the outbreak was likely perpetuated by carbapenem resistance genes being shared among unrelated bacteria via plasmids or other mobile genetic elements.

"This demonstrates the important role whole genome sequencing can play in investigating HAI outbreaks," said Richard Stanton, "This outbreak shows us how drug resistance genes can be shared among otherwise unrelated bacteria co-existing in a patient's microbial community or in the environment." This in turn may require expanding infection control and detection efforts to include multiple strains and species to halt the outbreak.

The bacteria involved in this outbreak included Klebsiella pneumonia and Escherichia coli, two species of bacteria that can cause a variety of healthcare-associated infections, including pneumonia, bloodstream infections, surgical site infections, and meningitis. Treatment of the infections in these outbreaks was complicated due to the presence of carbapenemase genes in the bacteria, of which two major variants of the Klebsiella pneumonia Carbapenemase (KPC) gene (KPC-2 and KPC-3) were found.

The bacterial strains with the KPC-2 gene were largely unrelated but all carried the same drug resistance plasmid. Similarly, the strains with the KPC-3 gene were quite diverse except they all shared a plasmid, common among the KPC-3 strains but different from the KPC-2 strains.

"Due in part to this finding, HAI investigations now include a broader scope to look not just for single species causing infections, but also for plasmids spreading drug resistance across multiple types of bacteria," said Dr. Stanton. Infection control efforts also focus on areas where plasmid sharing is likely to occur in the healthcare environment, such as in sinks and drains.

Vaneet Arora, Lorrie Sims, and Rachel Zinner from the Kentucky Department for Public Health isolated and cultured the bacterial samples used in this study. Jonathan Daniels, Alison Laufer Halpin, and Richard Stanton from the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention performed whole genome sequencing and analysis of the isolates.

This work was made possible through CDC's investments to Combat Antibiotic Resistant Bacteria and the Advanced Molecular Detection Program at CDC. A poster highlighting this work will be presented by Richard Stanton at the ASM Microbe 2018 conference in Atlanta, GA on June 10th from 12:45 - 2:45 PM, as part of Session 420 - Infection Prevention and Control: Drug-Resistant Pathogens in Hospitals.

Credit: 
American Society for Microbiology

Treg cells protect babies from getting HIV infection from their mothers

June 10, 2018 - Atlanta, GA - Scientists now report that Treg cells, a type of regulatory lymphocyte, may be protecting babies in the womb from getting infected with the HIV virus when the mother is infected. The research, from the Emory Vaccine Center, is presented at ASM Microbe, the American Society for Microbiology's annual meeting, held from June 7th through 11th in Atlanta, Georgia.

"Finding out what protects the majority of babies is important, as it can lead to ways to boost natural immune responses and make individuals resistant to HIV infection, said Peter Kessler, laboratory intern with the Emory University School of Medicine. Scientists had been puzzled for years by the fact that only a minority of babies born to mothers with HIV infection get the infection from their mothers. Currently, HIV infection can be successfully managed with antiretroviral drugs, but these drugs have to be given for life. Preventing the infection is very important, but there is no vaccine available yet.

Kessler and his colleagues from the Emory Vaccine Center found that levels of Treg lymphocytes were higher in the blood of newborn babies born to mothers with HIV infection who had escaped the infection themselves, compared with babies who were born with HIV infection.

Lymphocytes are cells of the immune system that protect the body by fighting bacteria and viruses. Treg cells, or regulatory T cells, are an important "self-check" in the immune system to prevent excessive immune reactions that could lead to tissue damage.

The researchers examined the blood of 64 babies who were born HIV-uninfected and 28 babies born HIV-infected and found that Treg cell levels were higher in uninfected babies at the time of birth. In contrast, other lymphocyte types were activated and higher in HIV-infected infants. The HIV virus can only infect cells that are activated, so Treg may protect from HIV infection by suppressing activation of other lymphocytes.

They analyzed the stored blood by flow cytometry, a technique that can differentiate between the different types of cells based on what markers they express on their surface. Regulatory T cells come in many forms with the most well-understood being those that express the markers CD4, CD25, and FOXP3.

"Even though the number of babies studied is relatively small, these findings indicate that Treg, by controlling immune activation, may lower the vulnerability of the babies to HIV or other chronic infections even before they are born," said Kessler. These results could pave the way for the development of vaccines or other immune-based therapies that could be used together with medications to prevent the spread of HIV or other infections from mothers to their babies.

A poster highlighting their work will be presented by Peter Kessler at the ASM Microbe 2018 meeting in Atlanta, GA, on June 10, 2018, 12:45-2:45 pm. The mothers and babies in this study were part of a CDC-funded clinical study in Malawi that looked at ways to prevent the spread of HIV from mothers to their babies during childbirth and breastfeeding.

Additional authors on this study are Surinder Kaur and Chris Ibegbu from the Emory Vaccine Center

Credit: 
American Society for Microbiology

Bacteriophages: Are they an overlooked driver of Parkinson's disease?

June 10, 2018 - Atlanta, GA - In the first study of its kind, researchers from the New York-based Human Microbiology Institute have discovered the role certain bacteriophages may play in the onset of Parkinson's disease (PD). The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7th to June 11th in Atlanta, Georgia.

The researchers, led by George, Tetz, M.D., Ph.D., Human Microbiology Institute, showed that the abundance of lytic Lactococcus phages was higher in PD patients when compared to healthy individuals. This abundance led to a 10-fold reduction in neurotransmitter-producing Lactococcus, suggesting the possible role of phages in neurodegeneration. Comparative analysis of the bacterial component also revealed significant decreases in Streptococcus spp. and Lactobacillus spp. in PD.

Lactococcus are regulators of gut permeability and are enteric dopamine producers, which plays a primary role in PD. "The depletion of lactococcus due to high numbers of strictly lytic phages in PD patients might be associated with PD development and directly linked to dopamine decrease as well as the development of gastrointestinal symptoms of PD," said Dr. Tetz.

To explore bacterial and bacteriophage community compositions associated with PD, the researchers used shotgun metagenomics sequencing data of fecal microbiome from 32 patients with PD and 28 controls.

The results indicate that the decrease in Lactococci in the PD patients was due to the appearance of strictly lytic, virulent lactococcal phages belonging to the c2-like and 936 groups that are frequently isolated from dairy products. These results open a discussion on the role of environmental phages and phagobiota composition in health and disease.

"Bacteriophages have previously been overlooked as pathogenic factors, and the study points out their pivotal role in pathogenesis," said Dr. Tetz. Future research is needed to explore bacterial viruses as a diagnostic and treatment target for therapeutic intervention.

Credit: 
American Society for Microbiology

Childhood obesity: Insights on risk factors and prevention

The factors that contribute to overweight and obesity are complex, but one pattern is clear: having obesity during childhood increases the likelihood of having obesity as an adult. The Nutrition 2018 meeting will feature new research on factors that may contribute to childhood obesity, as well as factors that can help kids maintain a healthy weight.

Nutrition 2018 is the inaugural flagship meeting of the American Society for Nutrition held June 9-12, 2018 at the Hynes Convention Center in Boston. Contact the media team for abstracts, images and interviews, or to obtain a free press pass to attend the meeting.

Trends in obesity prevalence

Latest stats show continued increase in obesity rates

While obesity has been on the rise for decades in the US, the proportion of Americans who are obese appeared to have reached a plateau more recently. A new analysis suggests that this leveling off was temporary, lasting from 2009-2012, and indicates that obesity rates have since continued to climb in both children and adults. If current trends continue, researchers project that by 2030, one-third of America's children age 6-11 and half of adolescents age 12-19 will be overweight or obese. Youfa Wang, Ball State University, will present this research on Monday, June 11, from 4:15-4:30 p.m. in the Hynes Convention Center, Room 311 (abstract).

New insights on risk factors

Mounting evidence that sugar-sweetened beverages are a risk factor for childhood obesity

A study that tracked more than 700 kids from the toddler to teen years finds intake of sugar-sweetened beverages was associated with a significantly higher body mass index (BMI) throughout childhood, while intake of milk, 100% juice and water-based sugar-free beverages was not associated with any difference in BMI. As one of the first longitudinal studies to examine children's beverage consumption over time, the study bolsters the evidence that sugar-sweetened beverages are an important risk factor for obesity. Teresa A. Marshall, College of Dentistry, University of Iowa, will present this research on Saturday, June 9, from 2-2:15 p.m. in the Hynes Convention Center, Room 309 (abstract).

Promoting healthy weight

Characteristics of successful programs to promote healthy weight among middle schoolers

Many programs and policies have been implemented to curb overweight and obesity rates in children and teens. New research takes a broad look at the outcomes of such programs to understand which factors seem to be associated with greatest success. Examples of impactful interventions include the use of scratch cooking for preparing school meals, not using physical activity for discipline at school and promoting drinking water at school. Lorrene D. Ritchie, Nutrition Policy Institute, University of California, will present this research on Monday, June 11, from 10:30-10:45 a.m. in the Hynes Convention Center, Room 306 (abstract).

Eating breakfast can help kids meet dietary recommendations

Kids in America eat a wide variety of morning foods, from cereal and milk to pancakes and pastries to eggs and fruit. In a new study funded by the Kellogg Company, kids who ate breakfast generally showed higher daily consumption of recommended nutrients including fiber, calcium, vitamin D and potassium, as well as greater whole grain and lower added sugar intake compared to those who did not eat in the morning. In particular, consuming grain-based foods with milk for breakfast was linked with several health benefits. Yanni Papanikolaou, Nutritional Strategies, will present this research on Sunday, June 10, from 8 a.m.-6 p.m. in the Hynes Convention Center, Exhibit Hall D (poster 800) (abstract).

Please note that abstracts presented at Nutrition 2018 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

Credit: 
American Society for Nutrition

Kitchen towels could contribute to the growth of potential pathogens that cause food poisoning

June 9, 2018 - Atlanta, GA - Researchers from the University of Mauritius have shown that factors such as family size, type of diet, multi-usage of towels, among other factors, impact the growth of pathogens on kitchen towels, potentially causing food poisoning. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology, held from June 7th to June 11th in Atlanta, Georgia.

"Our study demonstrates that the family composition and hygienic practices in the kitchen affected the microbial load of kitchen towels," said Dr. Biranjia-Hurdoyal."We also found that diet, type of use and moist kitchen towels could be very important in promoting the growth of potential pathogens responsible for food poisoning," she said.

49% of the kitchen towels collected in the study had bacterial growth which increased in number with extended family, presence on children and increasing family size. The towels for multipurpose usage (wiping utensils, drying hands, holding hot utensils, wiping/cleaning surfaces) had a higher bacterial count than single-use towels and humid towels showed higher bacterial count than the dry ones. Out of the 49 samples which were positive for bacterial growth, 36.7% grew coliforms, 36.7% Enterococcus spp and 14.3% S. aureus.

"In this study, we investigated the potential role of kitchen towels in cross-contamination in the kitchen and various factors affecting the microbial profile and load of kitchen towels," said Dr. Susheela D. Biranjia-Hurdoyal, Senior Lecturer, Department of Health Sciences, University of Mauritius, lead author on the study.

A total of 100 kitchen towels were collected after one month of use. The researchers cultured the bacteria and identified them by standard biochemical tests. They also determined the bacterial load on the towels.

S. aureus was isolated at a higher rate from families of lower socio-economic status and those with children. The risk of having coliforms (Escherichia coli) was higher from humid towels than the dried ones, from multipurpose towels than single-use ones and from families on non-vegetarian diets.

Coliform and S. aureus were detected at significantly higher prevalence from families with non-vegetarian diets. Escherichia coli is a normal flora of human intestine and it is released in large numbers in human feces. The presence of Escherichia coli indicates possible fecal contamination and lack of hygiene practices.

"The data indicated that unhygienic practices while handling non-vegetarian food could be common in the kitchen," said Dr. Biranjia-Hurdoyal. The presence of potential pathogens from the kitchen towels indicates that they could be responsible for cross-contamination in the kitchen and could lead to food poisoning. "Humid towels and multipurpose usage of kitchen towels should be discouraged. Bigger families with children and elderly members should be especially vigilant to hygiene in the kitchen," she said.

Credit: 
American Society for Microbiology

Loneliness is bad for the heart

Dublin, Ireland - 9 June 2018: Loneliness is bad for the heart and a strong predictor of premature death, according to a study presented today at EuroHeartCare 2018, the European Society of Cardiology's annual nursing congress.1 The study found that feeling lonely was a stronger predictor of poor outcomes than living alone, in both men and women.

"Loneliness is more common today than ever before, and more people live alone," said Anne Vinggaard Christensen, study author and PhD student, The Heart Centre, Copenhagen University Hospital, Denmark.2 "Previous research has shown that loneliness and social isolation are linked with coronary heart disease and stroke, but this has not been investigated in patients with different types of cardiovascular disease."3

The study investigated whether poor social network was associated with worse outcomes in 13,463 patients with ischaemic heart disease, arrhythmia (abnormal heart rhythm), heart failure, or heart valve disease. Data from national registers was linked with the DenHeart survey, which asked all patients discharged from April 2013 to April 2014 from five heart centres in Denmark to answer a questionnaire about their physical and mental health, lifestyle factors such as smoking, and social support.

Social support was measured using registry data on living alone or not, and survey questions about feeling lonely - Do you have someone to talk to when you need it? Do you feel alone sometimes even though you want to be with someone? "It was important to collect information on both, since people may live alone but not feel lonely while others cohabit but do feel lonely," explained Ms Vinggaard Christensen.

Feeling lonely was associated with poor outcomes in all patients regardless of their type of heart disease, and even after adjusting for age, level of education, other diseases, body mass index, smoking, and alcohol intake. Loneliness was associated with a doubled mortality risk in women and nearly doubled risk in men. Both men and women who felt lonely were three times more likely to report symptoms of anxiety and depression, and had a significantly lower quality of life than those who did not feel lonely.

"Loneliness is a strong predictor of premature death, worse mental health, and lower quality of life in patients with cardiovascular disease, and a much stronger predictor than living alone, in both men and women," said Ms Vinggaard Christensen.

Ms Vinggaard Christensen noted that people with poor social support may have worse health outcomes because they have unhealthier lifestyles, are less compliant with treatment, and are more affected by stressful events. But she said: "We adjusted for lifestyle behaviours and many other factors in our analysis, and still found that loneliness is bad for health."

She concluded: "We live in a time when loneliness is more present and health providers should take this into account when assessing risk. Our study shows that asking two questions about social support provides a lot of information about the likelihood of having poor health outcomes."

European guidelines on cardiovascular prevention state that people who are isolated or disconnected from others are at increased risk of developing and dying prematurely from coronary artery disease. The guidelines recommend assessment of psychosocial risk factors in patients with established cardiovascular disease and those at high risk of developing cardiovascular disease.4

Credit: 
European Society of Cardiology

New hope from the 'seven year switch' in Type 1 diabetes

New research has shown that the rapid decline in insulin production that causes type 1 diabetes continues to fall over seven years and then stabilises.

A team at the University of Exeter Medical School found evidence that the amount of insulin produced declines by almost 50% each year for seven years. At that point, the insulin levels stabilise.

The finding is a major step forward in understanding Type 1 diabetes and contradicts previous beliefs that the insulin produced by people with the condition drops relentlessly with time. It offers the hope that by understanding what changes after seven years, new strategies could be developed to preserve insulin secreting beta-cells in patients.

The study, published in Diabetes Care, measured C-peptide, which is produced at the same time and in the same quantities as the insulin that regulates our blood sugar. By measuring C-peptide levels in blood or in urine, scientists can tell how much insulin a person is producing themselves, even if they are taking insulin injections as treatment. The team studied 1,549 people with Type 1 diabetes from Exeter, England and Tayside, Scotland in the UNITED study.

Dr Beverley Shields, at the University of Exeter Medical School, who led the research, said: "This finding is really exciting. It suggests that a person with Type 1 diabetes will keep any working beta-cells they still have seven years after diagnosis. We are not sure why this is; it may well be that there is a small group of "resilient" beta-cells resistant to immune attack and these are left after all the "susceptible" beta-cells are destroyed. Understanding what is special about these "resilient" beta-cells may open new pathways to treatment for Type 1 diabetes."

Type 1 diabetes affects around 400,000 people in the UK. The disease commonly starts in childhood but can develop at any age, and causes the body's own immune system to attack and destroy the insulin-producing cells in the pancreas, leaving the patient dependent on life-long insulin injections.

Professor Andrew Hattersley, a Consultant in Diabetes at the Royal Devon and Exeter Hospital and Research Professor at the University of Exeter Medical School, looked forward. "Now we know there is a "seven year switch", the next question is why? Has the immune attack stopped or are we left with "super beta-cells" that can resist the immune onslaught. Any insights into halting the relentless destruction of the precious insulin-producing cells are valuable. We could not have made this progress without the help of over 1,500 patients. We owe it to them to try to find answers that might help patient care quickly."

Karen Addington, UK Chief Executive of the type 1 diabetes charity JDRF, said: "These results provide further evidence that the immune system's assault on insulin-producing beta cells is not as complete as we once believed - and may change over time. This further opens the door to identifying ways to preserve insulin production in people diagnosed with or living with type 1 diabetes."

Credit: 
University of Exeter

Science of racism examined in new set of research articles

White supremacist marches and xenophobic Twitter rants have brought overt racism to the center of public attention in recent months. Even still, subtle, structural, and systemic forms of racism continue to lurk in what is becoming an increasingly racially diverse United States. In a new collection of scholarly articles, psychological scientists describe research on the enduring and often hidden presence of racism at both the interpersonal and societal levels.

The articles are published in a special issue of Current Directions in Psychological Science, a journal of the Association for Psychological Science. Yale University professor Jennifer Richeson, who has earned multiple awards and honors for her research on intergroup relations, including a MacArthur Genius Award, is editor of the special issue.

"Although a special issue is decidedly insufficient to cover all of the emerging research on the psychology of racism, the papers included here are poised to better position psychological science to inform and shape more thoughtful discourse regarding the nature of racism, how it affects individual cognition and health, and, importantly, how best to combat it," Richeson writes in her introduction to the issue.

In one article, Richeson, with lead author Maureen Craig of New York University, and Julian Rucker of Yale University, highlight research showing the perceived threat that many White people feel when they anticipate increases in the of population of minorities. These perceptions can generate prejudice, discrimination, and anti-immigration sentiments. Future research should examine how resistance to demographic changes can be tempered (or worsened) by the rise in intergroup interactions that will occur as neighborhoods and communities grow more diverse, the authors say.

Other articles in the issue review research examining how individuals and societies sustain racial disparities. Studies have shown that White people often cloak or deny their privileged position by, for example, underestimating their advantages in wealth and employment. Even the egalitarian "color-blind" ideology often embraced in schools and workplaces can reduce sensitivity to racism and the unique needs of minorities. Research suggests that learning about racial disparities, such as the disproportionate number of Black individuals in prison, can prompt people to associate Blackness with crime and, consequently, lead them to justify existing crime policies.

Several articles in the issue address research on ethnic/racial identity and psychological health, cultural patterns and institutional realities that support racism, and the association between discrimination and physical health among African Americans.

One theme throughout the articles is the power of positive interactions between majority and marginalized groups. The more that White individuals interact with people of other races and ethnicities, the less threatened they feel by changing demographics and the more invested they become in the well-being of those groups, research suggests. But, the continuing persistence of racial segregation in neighborhoods, schools, and the like limits the potential for such contact to take place. There is also evidence indicating that the endorsement of multiculturalism -- as opposed to color-blindness -- is an effective way to lower prejudice (although some studies show negative effects such as heightened racial stereotyping).

Some of the foremost scholars on racism and diversity contributed to the collection, including Stanford University professor Jennifer Eberhardt, whose work on racial disparities in criminal justice earned her a MacArthur Genius Award; Victoria Plaut, a University of California, Berkeley professor widely recognized for her research on multiculturalism and diversity; Fordham University professor Tiffany Yip, who studies ethnic identity and academic outcomes; and Linda Tropp, an Emory University professor who studies intergroup relations.

The special issue is available free to the public at http://journals.sagepub.com/toc/cdp/current

Credit: 
Association for Psychological Science

Ten thousand bursting genes

image: Intron seqFISH enables 3D reconstruction of nascent transcription active sites (colored spots) in an embryonic stem cell (blue), with individual chromosomes occupying distinct spatial territories (colored differently). Here, 982 transcription active sites, corresponding to individual genes, are present in this cell.

Image: 
Cai laboratory / Cell

A breakthrough new technique enables scientists to image 10,421 genes at once within individual cells.

The work was done in the laboratory of Long Cai, research professor in biology and an affiliated faculty member of the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. A paper describing the research appears in the June 7 issue of the journal Cell.

The new technique, dubbed intron seqFISH (sequential fluorescence in situ hybridization), is a major advance in being able to identify what goes on across the genome in hundreds of different cells at once. Previously, researchers could only image four to five genes at a time in cells with microscopy. This work builds off of previous advances from the Cai laboratory, including an earlier version of seqFISH from 2014 and research from 2017 that profiled over 10,000 genes under a microscope. Scaling seqFISH up to a genomic level now enables the imaging of over 10,000 genes--about half of the total number of genes in mammals--within single cells.

In order for genetic instructions to be turned into an actual functioning protein, a process called transcription must first occur. This process often occurs in pulses, or "bursts." First, a gene will be read and copied into a precursor messenger RNA, or pre-mRNA, like jotting a quick, rough draft. This molecule then matures into a messenger RNA, or mRNA, akin to editing the rough draft. During the "editing" process, certain regions called introns are cut out of the pre-mRNA.

The team chose to focus on labeling introns because they are produced so early in the transcription process, giving a picture of what a cell is doing at the precise moment of gene expression.

Using the newly developed intron seqFISH technique, each intron is labeled with a unique fluorescent barcode, enabling it to be seen with a microscope. Seeing introns reveals which genes are currently turned on in individual cells, how strongly they are expressed, and where they are located. 10,421 introns--and therefore 10,421 genes--can be imaged at once.

Previous work that developed the barcoding technique focused on labeling mRNA itself, providing a measurement of how gene expression changed over several hours as the mRNA developed. Looking at introns enabled the researchers to examine, for the first time, so-called nascent transcriptomes--newly synthesized gene expression. This led them to discover that the transcription of genes oscillates globally across many genes on what Cai calls a "surprisingly short" timescale--only about two hours--compared to the time it takes for a cell to divide and replicate itself, which takes from 12 to 24 hours. This means that over the course of a two-hour period, many genes within a cell will burst on and off.

There are several reasons why the oscillation phenomenon had not been observed previously. First, because these two-hour oscillations are not synchronized amongst different cells, the fluctuations are averaged out by methods that require many cells. Second, the high accuracy of the seqFISH method allows the researchers to be certain that what they observe represents real biological fluctuations, rather than technical noise. Lastly, these two-hour oscillations are obscured when mRNAs rather than introns are measured, because mRNA molecules have a longer lifetime, three to four hours, in mammalian cells.

Additionally, because introns stay where the gene is physically located, fluorescently imaging introns allows researchers to visualize where genes are located within the chromosome, the large structure that DNA folds into within the cell's nucleus. In this work, the team was surprised to discover that most active, protein-encoding genes are located on the surface of the chromosome, not buried inside of it.

"This technique can be applied to any tissue," says Cai, who is a collaborator on the Human Cell Atlas, a project that aims to define all cell types in the human body. "Intron seqFISH can help identify cell types and also what the cells are going to do, in addition to giving us a look at the chromosome structure in the same cells."

Credit: 
California Institute of Technology