Papuans, the indigenous peoples of New Guinea Island, owe up to 5% of their genome to Denisovans, an extinct group closely related to Neanderthals who are known only by their DNA and sparse remains in Siberia and Tibet. To better understand the significance of this genetic contribution, researchers searched the genomes of 56 Papuan individuals to see if they carried Denisovan or Neanderthal DNA sequences, and then predicted how those sequences might affect the functioning of different types of cells.

Based on the location of the non-human sequences, the team found that in Papuans, Denisovan DNA — but not Neanderthal DNA — appears to strongly and consistently affect immune cells and functions. Further testing in cell cultures confirmed that Denisovan DNA sequences successfully regulated nearby genes, turning their expression up or down in ways that could affect how people respond to infections.

The new study suggests that Denisovan DNA sequences altered the immune response in early modern humans living in New Guinea and nearby islands, potentially helping them adapt to their local environment. The researchers conclude that further exploring how DNA from extinct human ancestors affects gene expression may be the key to understanding the consequences of interbreeding between ancient humans and other groups. The results also support the idea that archaic DNA has had a broad impact in shaping the genetic diversity and evolution of modern humans, and has likely affected multiple characteristics in people who inherited Denisovan and Neanderthal DNA.

Dr. Davide Vespasiani, first author, adds, “We show that not only Neanderthal, but also Denisovan DNA is very likely to contribute to gene expression in human populations. Further validations will reveal whether these effects are mostly cell type specific or consistent across cells.”

Dr. Irene Gallego Romero, senior author, concludes, “Some of the Denisovan DNA that has persisted in Papuan individuals until today plays a role in regulating genes involved in the immune system. Our study is the first to comprehensively shed light on the functional legacy of Denisovan DNA in the genomes of present-day humans.”

Story Source:

Materials provided by PLOS. Note: Content may be edited for style and length.

Antibiotic resistance is one of the leading causes of death and hospitalization worldwide. While the major drivers of antibiotic resistance are the overuse and misuse of antibiotics, natural elements such as heavy metals can also promote antibiotic resistance.

In the new study, researchers collected water and stool samples from both mothers and young children of 100 families in two rural subdistricts in Bangladesh. Families in the Hajiganj subdistrict use drinking water from shallow tube wells, which have a high concentration of arsenic, while Matlab families collect their drinking water from arsenic-free deep tube wells.

The median arsenic concentration in the 50 water samples from Hajiganj was 481 μg/L while the median arsenic concentration in the 50 water samples from Matlab was 0 μg/L. Overall, 84% of all water and stool samples across both sites were found to be positive for E. coli. Prevalence of antibiotic resistant E. coli was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p<0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p<0.05), but not among mothers. Moreover, a higher proportion of E. coli from Hajiganj were resistant to multiple antibiotics, including penicillin, cephalosporin, and chloramphenicol.

“The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure,” the authors say.

Dr. Islam adds, “Heavy metals such as arsenic are more stable than antibiotics in the environment, and they continue to exert selective pressure on bacteria over a more extended period driving the evolution and expansion of antimicrobial resistance in the community. The extent to which this phenomenon drives the observed higher rates of antimicrobial resistance, as opposed to other confounders, would benefit from further study; nevertheless, it is critical to contain this environmental driver of antimicrobial resistance along with responsible antimicrobial usage in medicine and agriculture.”

Story Source:

Materials provided by PLOS. Note: Content may be edited for style and length.

Along with producing anxiety in the mice who consumed aspartame, the effects extended up to two generations from the males exposed to the sweetener. The study is published in the Proceedings of the National Academy of Sciences.

“What this study is showing is we need to look back at the environmental factors, because what we see today is not only what’s happening today, but what happened two generations ago and maybe even longer,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.

The study came about, in part, because of previous research from the Bhide Lab on the transgenerational effects of nicotine on mice. The research showed temporary, or epigenetic, changes in mice sperm cells. Unlike genetic changes (mutations), epigenetic changes are reversible and don’t change the DNA sequence; however, they can change how the body reads a DNA sequence.

“We were working on the effects of nicotine on the same type of model,” Bhide said. “The father smokes. What happened to the children?”

The U.S. Food and Drug Administration (FDA) approved aspartame as a sweetener in 1981. Today, nearly 5,000 metric tons are produced each year. When consumed, aspartame becomes aspartic acid, phenylalanine and methanol, all of which can have potent effects on the central nervous system.

Led by doctoral candidate Sara Jones, the study involved providing mice with drinking water containing aspartame at approximately 15% of the FDA-approved maximum daily human intake. The dosage, equivalent to six to eight 8-ounce cans of diet soda a day for humans, continued for 12 weeks in a study spanning four years.

Pronounced anxiety-like behavior was observed in the mice through a variety of maze tests across multiple generations descending from the aspartame-exposed males.

“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” Jones said. “It was completely unexpected. Usually you see subtle changes.”

When given diazepam, a drug used to treat anxiety disorder in humans, mice in all generations ceased to show anxiety-like behavior.

Researchers are planning an additional publication from this study focused on how aspartame affected memory. Future research will identify the molecular mechanisms that influence the transmission of aspartame’s effect across generations.

Other co-authors were Department of Biomedical Sciences faculty members Deirdre McCarthy, Cynthia Vied and Gregg Stanwood, and FSU Department of Psychology Professor Chris Schatschneider.

This research was supported by the Jim and Betty Ann Rodgers Chair Fund at Florida State University and by the Bryan Robinson Foundation.

Story Source:

Materials provided by Florida State University. Original written by Robert Thomas. Note: Content may be edited for style and length.