Posts Tagged ‘science’


Whiile human genetic mutations are involved in a small number of Parkinson’s disease (PD) cases, the vast majority of cases are of unknown environmental causes, prompting enormous interest in identifying environmental risk factors involved. The link between Helicobacter pylori (H. pylori) and gastric ulcers has been known for several decades, but new evidence suggests that this harmful bacterium may play a role in PD as well. A new review in the Journal of Parkinson’s Disease summarizes the current literature regarding the link between H. pylori and PD and explores the possible mechanisms behind the association.

In a comprehensive review of prior studies, investigators uncovered four key findings:

People with PD are 1.5-3-fold more likely to be infected with H. pylori than people without PD.
H. pylori-infected PD patients display worse motor functions than H. pylori-negative PD patients.
Eradication of H. pylori improved motor function in PD patients over PD patients whose H. pylori was not eradicated.
Eradication of H. pylori improved levodopa absorption in PD patients compared to PD patients whose H. pylori was not eradicated.
“This is an in-depth and comprehensive review that summarizes all the major papers in the medical literature on Parkinson’s disease and H. pylori, the common stomach bacterium that causes gastritis, ulcers and stomach cancer,” explained lead investigator David J. McGee, PhD, Associate Professor, Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, Shreveport, LA, USA. “Our conclusion is that there is a strong enough link between the H. pylori and Parkinson’s disease that additional studies are warranted to determine the possible causal relationship.”

Investigators also analyzed existing studies to try and find possible testable pathways between the bacterial infection and Parkinson’s to lay the groundwork for future research. They found four main possible explanations for the association:

Bacterial toxins produced by H. pylori may damage neurons.

The infection triggers a massive inflammatory response that causes damage to the brain.

H. pylori may disrupt the normal gut microbial flora.

The bacteria might interfere with the absorption properties of levodopa, the medication commonly used to treat the symptoms of Parkinson’s disease.

The onset of PD is often preceded by gastrointestinal dysfunction, suggesting that the condition might originate in the gut and spread to the brain along the brain-gut axis. In the review, investigators note that this has been documented in rats.

Screening PD patients for the presence of H. pylori and subsequent treatment if positive with anti-H. pylori triple drug therapy, may contribute to improved levodopa absorption and ultimately improvement of PD symptoms, potentially leading to a longer life span in patients with PD.

“Evidence for a strong association among H. pylori chronic infection, peptic ulceration and exacerbation of PD symptoms is accumulating,” concluded Dr. McGee.

“However, the hypotheses that H. pylori infection is a predisposing factor, disease progression modifier, or even a direct cause of PD remain largely unexplored. This gut pathology may be multifactorial, involving H. pylori, intestinal microflora, inflammation, misfolding of alpha-synuclein in the gut and brain, cholesterol and other metabolites, and potential neurotoxins from bacteria or dietary sources. Eradication of H. pylori or return of the gut microflora to the proper balance in PD patients may ameliorate gut symptoms, L-dopa malabsorption, and motor dysfunction.”


by Alison Abbott

It had been hiding in plain sight. The original letter — long thought lost — in which Galileo Galilei first set down his arguments against the church’s doctrine that the Sun orbits the Earth has been discovered in a misdated library catalogue in London. Its unearthing and analysis expose critical new details about the saga that led to the astronomer’s condemnation for heresy in 1633.

The seven-page letter, written to a friend on 21 December 1613 and signed “G.G.”, provides the strongest evidence yet that, at the start of his battle with the religious authorities, Galileo actively engaged in damage control and tried to spread a toned-down version of his claims.

Many copies of the letter were made, and two differing versions exist — one that was sent to the Inquisition in Rome and another with less inflammatory language. But because the original letter was assumed to be lost, it wasn’t clear whether incensed clergymen had doctored the letter to strengthen their case for heresy — something Galileo complained about to friends — or whether Galileo wrote the strong version, then decided to soften his own words.

Galileo did the editing, it seems. The newly unearthed letter is dotted with scorings-out and amendments — and handwriting analysis suggests that Galileo wrote it. He shared a copy of this softened version with a friend, claiming it was his original, and urged him to send it to the Vatican.

The letter has been in the Royal Society’s possession for at least 250 years, but escaped the notice of historians. It was rediscovered in the library there by Salvatore Ricciardo, a postdoctoral science historian at the University of Bergamo in Italy, who visited on 2 August for a different purpose, and then browsed the online catalogue.

“I thought, ‘I can’t believe that I have discovered the letter that virtually all Galileo scholars thought to be hopelessly lost,’” says Ricciardo. “It seemed even more incredible because the letter was not in an obscure library, but in the Royal Society library.”

Ricciardo, together with his supervisor Franco Giudice at the University of Bergamo and science historian Michele Camerota of the University of Cagliari, describe the letter’s details and implications in an article in press at the Royal Society journal Notes and Records. Some science historians declined to comment on the finding before they had scrutinized the article. But Allan Chapman, a science historian at the University of Oxford, UK, and president of the Society for the History of Astronomy, says “it’s so valuable — it will allow new insights into this critical period”.

Mixed messages
Galileo wrote the 1613 letter to Benedetto Castelli, a mathematician at the University of Pisa in Italy. In it, Galileo set out for the first time his arguments that scientific research should be free from theological doctrine (see ‘The Galileo affair’).

He argued that the scant references in the Bible to astronomical events should not be taken literally, because scribes had simplified these descriptions so that they could be understood by common people. Religious authorities who argued otherwise, he wrote, didn’t have the competence to judge. Most crucially, he reasoned that the heliocentric model of Earth orbiting the Sun, proposed by Polish astronomer Nicolaus Copernicus 70 years earlier, is not actually incompatible with the Bible.

Galileo, who by then was living in Florence, wrote thousands of letters, many of which are scientific treatises. Copies of the most significant were immediately made by different readers and widely circulated.

His letter to Castelli caused a storm.

Of the two versions known to survive, one is now held in the Vatican Secret Archives. This version was sent to the Inquisition in Rome on 7 February 1615, by a Dominican friar named Niccolò Lorini. Historians know that Castelli then returned Galileo’s 1613 letter to him, and that on 16 February 1615 Galileo wrote to his friend Piero Dini, a cleric in Rome, suggesting that the version Lorini had sent to the Inquisition might have been doctored. Galileo enclosed with that letter a less inflammatory version of the document, which he said was the correct one, and asked Dini to pass it on to Vatican theologians.

His letter to Dini complains of the “wickedness and ignorance” of his enemies, and lays out his concern that the Inquisition “may be in part deceived by this fraud which is going around under the cloak of zeal and charity”.

At least a dozen copies of the version Galileo sent to Dini are now held in different collections.

The existence of the two versions created confusion among scholars over which corresponded to Galileo’s original.

Beneath its scratchings-out and amendments, the signed copy discovered by Ricciardo shows Galileo’s original wording — and it is the same as in the Lorini copy. The changes are telling. In one case, Galileo referred to certain propositions in the Bible as “false if one goes by the literal meaning of the words”. He crossed through the word “false”, and replaced it with “look different from the truth”. In another section, he changed his reference to the Scriptures “concealing” its most basic dogmas, to the weaker “veiling”.

This suggests that Galileo moderated his own text, says Giudice. To be certain that the letter really was written in Galileo’s hand, the three researchers compared individual words in it with similar words in other works written by Galileo around the same time.

Chance discovery
Ricciardo uncovered the document when he was spending a month this summer touring British libraries to study any handwritten comments that readers might have left on Galileo’s printed works. When his one day at the Royal Society was finished, he idly flicked through the online catalogue looking for anything to do with Castelli, whose writings he had recently finished editing.

One entry jumped out at him — a letter that Galileo wrote to Castelli. According to the catalogue, it was dated 21 October 1613. When Ricciardo examined it, his heart leapt. It appeared to include Galileo’s own signature, “G.G.”; was actually dated 21 December 1613; and contained many crossings out. He immediately realized the letter’s potential importance and asked for permission to photograph all seven pages.

“Strange as it might seem, it has gone unnoticed for centuries, as if it were transparent,” says Giudice. The misdating might be one reason that the letter has been overlooked by Galileo scholars, says Giudice. The letter was included in an 1840 Royal Society catalogue — but was also misdated there, as 21 December 1618.Another reason might be that the Royal Society is not the go-to place in the United Kingdom for this type of historical document, whose more natural home would have been the British Library.

The historians are now trying to trace how long the letter has been in the Royal Society library, and how it arrived there. They know that it has been there since at least the mid-eighteenth century, and they have found hints in old catalogues that it might even have been there a century or more earlier. The researchers speculate that it might have arrived at the society thanks to close connections between the Royal Society and the Academy of Experiments in Florence, which was founded in 1657 by Galileo’s students but fizzled out within a decade or so.

For now, the researchers are stunned by their find. “Galileo’s letter to Castelli is one of the first secular manifestos about the freedom of science — it’s the first time in my life I have been involved in such a thrilling discovery,” says Giudice.

1543 Polish astronomer Nicolaus Copernicus publishes his book On the Revolutions of the Heavenly Spheres, which proposes that the planets orbit the Sun.

1600 The Inquisition in Rome convicts Dominican friar and mathematician Giordano Bruno of heresy on multiple counts, including supporting and extending the Copernican model. Bruno is burnt at the stake.

1610 Galileo publishes his book The Starry Messenger (Sidereus nuncius), describing discoveries made with his newly built telescope that provide evidence for the Copernican model.

1613 Galileo writes a letter to his friend Benedetto Castelli, arguing against the doctrine of the Roman Catholic Church in matters of astronomy. Copies of this letter are circulated.

1615 Dominican friar Niccolò Lorini forwards a copy of the letter to the inquisition in Rome. Galileo asks a friend to forward what he claims to be a copy of his original letter to Rome; this version is less inflammatory than Lorini’s.

1616 Galileo is warned to abandon his support of the Copernican model. Books supporting the Copernican model are banned. On the Revolutions of the Heavenly Spheres is withdrawn from circulation pending correction to clarify that it is only a theory.

1632 Galileo publishes Dialogue Concerning the Two Chief World Systems, in which he lays out the various evidence for and against the Church’s Ptolemaic model of the Solar System, and the Copernican model. The Inquisition summons Galileo to Rome to stand trial.

1633 Galileo is convicted on “vehement suspicion of heresy” and the book is banned. He is issued with a prison sentence, later commuted to house arrest, under which lived the last nine years of his life.

Nature 561, 441-442 (2018)



A gene drive has successfully caused the collapse of a malaria-carrying mosquito population in the lab, researches report today (September 24) in Nature Biotechnology. This is the first time a gene drive—a genetic element that ensures its own inheritance—has caused a population of mosquitoes to self-destruct, a result that holds promise for combating malaria.

“This breakthrough shows that gene drive can work, providing hope in the fight against a disease that has plagued mankind for centuries,” study coauthor Andrea Crisanti, a molecular parasitologist at Imperial College London, says in a university statement.

In the study, the team targeted a region of a gene called doublesex that is responsible for female development. Female Anopheles gambiae mosquitoes with two copies of the altered doublesex gene did not lay eggs. After eight generations, the drive had spread through the entire population, such that no eggs were laid.

“It’s a really stunning development,” Omar Akbari, an entomologist at the University of California, Irvine who was not involved to the study, tells Wired, noting that mosquitoes are under “huge evolutionary pressure” to resist gene drives that cause the population to collapse. However, Akbari tells Science News that this gene drive might not work well in the wild because resistance will probably pop up.

Crisanti, however, is more confident. “We are not saying this is 100 percent resistance-proof,” he tells The New York Times. “But it looks very promising.” Still, he adds in the university statement, “[i]t will still be at least 5-10 years before we consider testing any mosquitoes with gene drive in the wild.” First, his team will need to test the gene drive in larger containers, where the mosquitoes can act more naturally, Crisanti tells Wired—swarming to find a mate, for instance. Such details were difficult to mimic in the 20 cubic centimeter cages used in this study.

Despite the need for further testing, some researchers hailed the current study as a major success. “With this achievement,” Kevin Esfelt, who studies the evolution of gene drives at MIT, tells The New York Times, “the major barriers to saving [human] lives are arguably no longer mostly technical, but social and diplomatic.”–gene-drive-wipes-out-lab-mosquitoes-64849



Previous research has shown that the gut-brain connection, which refers to signaling between the digestive and the central nervous systems, is based on the transport of hormones, but a study published today (September 21) in Science suggests there may be a more direct link—the vagus nerve.

This research presents “a new set of pathways that use gut cells to rapidly communicate with . . . the brain stem,” Daniel Drucker, who studies gut disorders at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, and was not involved with the project, tells Science.

Building on an earlier study in which the team found that gut cells had synapses, the researchers injected a rabies virus, expressing green fluorescence, into the stomachs of mice and watched it travel speedily from the intestines to the rodents’ brainstems.

When they grew sensory gut cells together with neurons from the vagus nerve, the neurons moved across the dish to form synapses with the gut cells and began electrically coupling with them. Adding sugar to the dish sped up the rate of signaling between the gut and brain cells, a finding that suggests glutamate, a neurotransmitter involved in sensing taste, may be key to the process. Blocking glutamate secretion in gut cells brought these signals to a grinding halt.

“We think these findings are going to be the biological basis of a new sense,” coauthor Diego Bohórquez, an assistant professor of medicine at Duke University School of Medicine, says in a statement. “One that serves as the entry point for how the brain knows when the stomach is full of food and calories. It brings legitimacy to idea of the ‘gut feeling’ as a sixth sense.”–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129



The protein Bmal1, which helps regulate the body’s internal clock, is found in especially high levels in the brain and in skeletal muscles. Mice completely deficient in Bmal1 were known to suffer from sleep impairments, but the specifics at play weren’t clear. At the University of California, Los Angeles, Ketema Paul and colleagues looked to these mice for clues about the role Bmal1 plays in sleep regulation.

When Paul’s team restored levels of the Bmal1 protein in the mice’s brains, their ability to rebound from a night of bad sleep remained poor. However, turning on production in skeletal muscles alone enabled mice to sleep longer and more deeply to recover after sleep loss.

For decades, scientists have thought sleep was controlled purely by the brain. But the new study indicates the ability to catch up on one’s sleep after a bout of sleeplessness is locked away in skeletal muscles, not the brain—at least for mice. “I think it’s a real paradigm shift for how we think about sleep,” says John Hogenesch, a chronobiologist at Cincinnati Children’s Hospital Medical Center who discovered the Bmal1 gene but was not involved in this study.

Paul’s group also found that having too much of the Bmal1 protein in their muscles not only made mice vigilant but also invulnerable to the effects of sleep loss, so that they remained alert even when sleep-deprived and slept fewer hours to regain lost sleep. “To me, that presents a potential target where you could treat sleep disorders,” says Paul, noting that an inability to recover from sleep loss can make us more susceptible to diseases.

The paper
J.C. Ehlen et al., “Bmal1 function in skeletal muscle regulates sleep,” eLife, 6:e26557, 2017.–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129

Senescent cells (represented here in green) no longer function but can broadcast inflammatory signals to the cells around them. These cells are implicated in a number of age-related diseases. Credit: The Mayo Clinic

Darren Baker, Ph.D., a Mayo Clinic molecular biologist and senior author of the paper, and first author Tyler Bussian, a Mayo Clinic Graduate School of Biomedical Sciences student.

Zombie cells are the ones that can’t die but are equally unable to perform the functions of a normal cell. These zombie, or senescent, cells are implicated in a number of age-related diseases. And with a new letter in Nature, Mayo Clinic researchers have expanded that list.

In a mouse model of brain disease, scientists report that senescent cells accumulate in certain brain cells prior to cognitive loss. By preventing the accumulation of these cells, they were able to diminish tau protein aggregation, neuronal death and memory loss.

“Senescent cells are known to accumulate with advancing natural age and at sites related to diseases of aging, including osteoarthritis; atherosclerosis; and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s,” says Darren Baker, Ph.D., a Mayo Clinic molecular biologist and senior author of the paper. “In prior studies, we have found that elimination of senescent cells from naturally aged mice extends their healthy life span.”

In the current study, the team used a model that imitates aspects of Alzheimer’s disease.

“We used a mouse model that produces sticky, cobweb like tangles of tau protein in neurons and has genetic modifications to allow for senescent cell elimination,” explains first author Tyler Bussian, a Mayo Clinic Graduate School of Biomedical Sciences student who is part of Dr. Baker’s lab. “When senescent cells were removed, we found that the diseased animals retained the ability to form memories, eliminated signs of inflammation, did not develop neurofibrillary tangles, and had maintained normal brain mass.” They also report that pharmacological intervention to remove senescent cells modulated the clumping of tau proteins.

Also, the team was able to identify the specific type of cell that became senescent, says Dr. Baker.

“Two different brain cell types called ‘microglia’ and ‘astrocytes’ were found to be senescent when we looked at brain tissue under the microscope,” says Bussian. “These cells are important supporters of neuronal health and signaling, so it makes sense that senescence in either would negatively impact neuron health.”

The finding was somewhat surprising, explains Dr. Baker, because at the time their research started, a causal link between senescent cells and neurodegenerative disease had not been established.

“We had no idea whether senescent cells actively contributed to disease pathology in the brain, and to find that it’s the astrocytes and microglia that are prone to senescence is somewhat of a surprise, as well,” says Dr. Baker.

In terms of future work, Dr. Baker explains that this research lays out the best-case scenario, where prevention of damage to the brain avoided the disease state. “Clearly, this same approach cannot be applied clinically, so we are starting to treat animals after disease establishment and working on new models to examine the specific molecular alterations that occur in the affected cells,” says Dr. Baker.

In addition to Dr. Baker and Bussian, the other authors are Asef Aziz, a medical student formerly at Mayo Clinic; Charlton Meyer, Mayo Clinic; Barbara Swenson, Ph.D., Mayo Clinic; and Jan van Deursen, Ph.D., Mayo Clinic. Dr. van Deursen is the Vita Valley Professor of Cellular Senescence. Drs. Baker and van Deursen are inventors on patents licensed to Unity Biotechnology by Mayo Clinic, and Dr. van Deursen is a co-founder of Unity Biotechnology.

Funding for this research was provided by the Ellison Medical Foundation, the Glenn Foundation for Medical Research, the National Institutes of Health, the Mayo Clinic Children’s Research Center, and the Alzheimer’s Disease Research Center of Mayo Clinic.


Weight gain trajectories in early childhood are related to the composition of oral bacteria of two-year-old children, suggesting that this understudied aspect of a child’s microbiota — the collection of microorganisms, including beneficial bacteria, residing in the mouth — could serve as an early indicator for childhood obesity. A study describing the results appears September 19 in the journal Scientific Reports.

“One in three children in the United States is overweight or obese,” said Kateryna Makova, Pentz Professor of Biology and senior author of the paper. “If we can find early indicators of obesity in young children, we can help parents and physicians take preventive measures.”

The study is part of a larger project with researchers and clinicians at the Penn State Milton S. Hershey Medical Center called INSIGHT, led by Ian Paul, professor of pediatrics at the Medical Center, and Leann Birch, professor of foods and nutrition at the University of Georgia. The INSIGHT trial includes nearly 300 children and tests whether a responsive parenting intervention during a child’s early life can prevent the development of obesity. It is also designed to identify biological and social risk factors for obesity.

“In this study, we show that a child’s oral microbiota at two years of age is related to their weight gain over their first two years after birth,” said Makova.

The human digestive tract is filled with a diverse array of microorganisms, including beneficial bacteria, that help ensure proper digestion and support the immune system. This “microbiota” shifts as a person’s diet changes and can vary greatly among individuals. Variation in gut microbiota has been linked to obesity in some adults and adolescents, but the potential relationship between oral microbiota and weight gain in children had not been explored prior to this study.

“The oral microbiota is usually studied in relation to periodontal disease, and periodontal disease has in some cases been linked to obesity,” said Sarah Craig, a postdoctoral scholar in biology at Penn State and first author of the paper. “Here, we explored any potential direct associations between the oral microbiota and child weight gain. Rather than simply noting whether a child was overweight at the age of two, we used growth curves from their first two years after birth, which provides a more complete picture of how the child is growing. This approach is highly innovative for a study of this kind, and gives greater statistical power to detect relationships.”

Among 226 children from central Pennsylvania, the oral microbiota of those with rapid infant weight gain — a strong risk factor for childhood obesity — was less diverse, meaning it contained fewer groups of bacteria. These children also had a higher ratio of Firmicutes to Bacteroidetes, two of the most common bacteria groups found in the human microbiota.

“A healthy person usually has a lot of different bacteria within their gut microbiota,” said Craig. “This high diversity helps protect against inflammation or harmful bacteria and is important for the stability of digestion in the face of changes to diet or environment. There’s also a certain balance of these two common bacteria groups, Firmicutes and Bacteroidetes, that tends to work best under normal healthy conditions, and disruptions to that balance could lead to dysregulation in digestion.”

Lower diversity and higher Firmicutes to Bacteroidetes (F:B) ratio in gut microbiota are sometimes observed as a characteristic of adults and adolescents with obesity. However, the researchers did not see a relationship of weight gain with either of these measures in gut microbiota of two-year-olds, suggesting that the gut microbiota may not be completely established at two years of age and may still be undergoing many changes.

“There are usually dramatic changes to an individual’s microbiota as they develop during early childhood,” said Makova. “Our results suggest that signatures of obesity may be established earlier in oral microbiota than in gut microbiota. If we can confirm this in other groups of children outside of Pennsylvania, we may be able to develop a test of oral microbiota that could be used in clinical care to identify children who are at risk for developing obesity. This is particularly exciting because oral samples are easier to obtain than those from the gut, which require fecal samples.”

Interestingly, weight gain in children was also related to diversity of their mother’s oral microbiota. This could reflect a genetic predisposition of the mother and child to having a similar microbiota, or the mother and child having a similar diet and environment.

“It could be a simple explanation like a shared diet or genetics, but it might also be related to obesity,” said Makova. “We don’t know for sure yet, but if there is an oral microbiome signature linked to the dynamics of weight gain in early childhood, there is a particular urgency to understand it. Now we are using additional techniques to look at specific species of bacteria–rather than larger taxonomic groups of bacteria–in both the mothers and children to see whether specific bacteria species influence weight gain and the risk of obesity.”

In addition to Makova, Craig, Paul, and Birch, the research team includes Jennifer Savage, Michele Marini, Jennifer Stokes, Anton Nekrutenko, Matthew Reimherr, and Francesca Chiaromonte from Penn State, Daniel Blankenberg from the Cleveland Clinic, and Alice Carla Luisa Parodi from Politecnico di Milano. INSIGHT (Intervention Nurses Start Infants Growing on Healthy Trajectories) is coordinated through the Penn State Milton S. Hershey Medical Center.

This work is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the Penn State Eberly College of Science; the Penn State Institute for Cyberscience; the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH); and the Pennsylvania Department of Health using Tobacco CURE funds.