Research uncovers key system in E. coli that could lead to new antibiotics

In addition to using the structure as a platform to generate antibiotics,
researchers can also use it to design new sensors of molecules of interest,
says Dr. Luis Rogelio (Roger) Cruz-Vera.
Image Credit: Michael Mercier | UAH

Research led by the University of Alabama in Huntsville (UAH) has for the first time identified the precise genetic operational structure of a key system in Escherichia coli (E. coli) bacteria, opening the door to possible new antibiotics to treat the infections it causes.

“The gene that we studied is involved in producing a bacterial hormone that is important for bacterial colonization. This hormone induces the production of sticky substances used by bacteria to adhere to inert surfaces, as well as plants and animal tissues,” says Dr. Luis Rogelio (Roger) Cruz-Vera, an associate professor in the Department of Biological Sciences at UAH, a part of the University of Alabama System.

“Our new structure will be used in future studies to obtain compounds that can modulate the production of this hormone in bacteria, reducing bacterial colonization by altering the bacterial cell’s capacity for attachment to surfaces and reduce communication with other cells.”

Most infectious E. coli cases are mild and result in vomiting, diarrhea, cramps, and fatigue, but some strains can cause severe illness and even life-threatening complications.

In 2015, Dr. Cruz-Vera teamed with Dr. Emily Gordon and Dr. Arnab Sengupta, both of whom were doctoral students in UAH’s Biotechnology Science and Engineering program at the time, and whose work during their graduate tenure produced the genetic and biochemical assays used in the research paper the trio wrote with other collaborators. The research was funded by the National Science Foundation.

Study finds Rwandan genocide chemically modified the DNA of victims and victims’ offspring

USF Professor Derek Wildman and Clarisse Mussanabaganwa,
visiting scholar from the University of Rwanda,
conduct research at USF.

Scientists with the USF Genomics program and the Center for Global Health and Infectious Disease Research have taken a significant step in providing the people of Rwanda the scientific tools they need to help address mental health issues that stemmed from the 1994 genocide of the Tutsi ethnic group.

In a first-of-its-kind study, Professors Monica Uddin and Derek Wildman of the College of Public Health looked at the entire genomes of Tutsi women who were pregnant and living in Rwanda at the time of the genocide and their offspring and compared their DNA to other Tutsi women pregnant at the same time and their offspring, who were living in other parts of the world.

In the study published in Epigenomics, they found that the terror of genocide was associated with chemical modifications to the DNA of genocide-exposed women and their offspring. Many of these modifications occurred in genes previously implicated in risk for mental disorders such as PTSD and depression. These findings suggest that, unlike gene mutations, these chemical “epigenetic” modifications can have a rapid response to trauma across generations.

“Epigenetics refers to stable, but reversible, chemical modifications made to DNA that help to control a gene’s function,” Uddin said. “These can happen in a shorter time frame than is needed for changes to the underlying DNA sequence of genes. Our study found that prenatal genocide exposure was associated with an epigenetic pattern suggestive of reduced gene function in offspring.”

An overuse of road salt in the winter has potentially harmful effects for everything from wildlife to groundwater

The winter months can bring dicey travel conditions, but those can be made safer with shovels, plows, and deicers like road salts. For road salts, a little can go a long way in improving safety, but its use is not without consequences. Researchers from the College of Agriculture, Health and Natural Resources and the College of Liberal Arts and Sciences are working to better understand the numerous environmental impacts of using too much salt on roads and walkways.

Bigger Frogs, More Mosquitos

Department of Natural Resources and the Environment researcher Tracy Rittenhouse and her group are investigating the effects road salts on amphibians.

“Previous research showed that tadpoles tend to metamorph larger in size from salty wetlands and high salinity conditions,” Rittenhouse says. “Generally, we think larger size as a good thing but we’re not sure why they’re larger or how they might be different physiologically.”

Rittenhouse explains that frogs starting life in saltier conditions, though larger, don’t seem to have any advantages later in life, whereas frogs from lower salt conditions started life smaller but grew much faster and larger over time. These results show that not only are amphibians amazingly tolerant to salt, but that we have much to learn. Despite the quantities of salt entering wetland environments, this resilience is why we have not seen massive declines in amphibian populations, says Rittenhouse.

Another experiment completed by an undergraduate student in her lab group showed that juvenile frogs not only detect if soil is salty, they will consistently avoid those conditions.

“That project opened up this whole arena of what we really should be looking at is the juvenile and adult frogs and how they might be responding to salinity in the terrestrial environment,” she says.

Researchers find low oxygen and sulfide in the oceans played greater role in ancient mass extinction

Seth Young’s research group collecting and describing limestone samples from a field site in the Roberts Mountains, Nevada.
Credit: Anders Lindskog/Florida State University

Florida State University researchers have new insight into the complicated puzzle of environmental conditions that characterized the Late Ordovician Mass Extinction (LOME), which killed about 85% of the species in the ocean.

Their work on the 445-million-year-old mass extinction event was published online in the journal AGU Advances.

“We found that reducing conditions — with low to no oxygen and little to no hydrogen sulfide levels — are probably playing a much more important role than we previously thought,” said lead author Nevin Kozik, a doctoral candidate in the Department of Earth, Ocean and Atmospheric Science and researcher at the FSU-headquartered National High Magnetic Field Laboratory. “If you imagine a pie chart of the causes of this extinction, we’re increasing that wedge that signifies oxygen deficiency, which is happening in concert with a cooling climate and widespread habitat loss due to sea-level change.”

The research is the first study to use measurements of multiple elements from several sites to examine the conditions that led to the LOME, the second-largest extinction event in the Earth’s history and the only mass extinction to occur during what are called icehouse conditions, when Earth’s climate is cold enough at the poles to support ice sheets year-round.

What you need to know about Pfizer’s anti COVID-19 drug Paxlovid

The FDA has authorized Pfizer’s Paxlovid for emergency use* to treat COVID-19 patients at high risk of hospitalization or death. Paxlovid can slow the replication of the virus that causes COVID, but it has the potential for dangerous interactions with drugs commonly prescribed for diabetes, heart disease, and many other conditions.

High risk patients are often those who have not been vaccinated, and/or have a number of comorbidities (additional, chronic health problems) such as hypertension, diabetes, hyperlipidemia, depression, and cancer.

Patients already taking multiple drugs to control chronic diseases, could be effected by harmful drug interactions between the their current drugs and Paxlovid. Awareness of potential drug-drug interactions may help to avoid severe adverse drug reactions and improve efficacy of Paxlovid’s anti-COVID-19 activity.

Paxloid contains two medicines in two separate tablets, nirmatrelvir and ritonavir. The drug’s anti-COVID-19 activity relies on the inhibition of SARS-CoV-2 Mpro enzyme activity by nirmatrelvir, which results in inhibition of virus replication. Nirmatrelvir is a substrate of cytochrome P450 CYP3A4 for metabolism.

Ritonavir is an HIV drug that inhibits CYP3A4 and slows the metabolism of Nirmatrelvir, therefore enhancing efficacy of anti-virus activity of Nirmatrelvir.

Spleen function discovery could lead to better treatments for infectious diseases

An advanced fluorescent microscopy image of the complex networks of stromal cells that construct the spleen and support immune responses.
Image: Professor Scott Mueller

Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have discovered a new gene that plays an important role in the way the spleen functions, potentially leading to new treatments for infectious diseases.

The study, published in Science Immunology, also uncovered multiple new spleen cells and revealed the distinct way they respond in order to fight off different infections.

The spleen plays a key role in the immune responses that protect the body against various diseases and infections such as virus infections, malaria and sepsis, and also plays a key role in the immune response to vaccines. However, it has not been known how the spleen functions to support this response.

University of Melbourne Professor Scott Mueller, a Laboratory Head at the Doherty Institute and lead author on the paper, explained that while it is known the spleen is made up of various networks of cells called fibroblasts, a clear picture of how these cells are constructed and function, was lacking.

“Using novel biological tools and next generation sequencing, we were able to examine precisely how specialized types of fibroblast cells dictate how the spleen works to protect against infections,” Professor Mueller explained.

Common clay materials may help curb methane emissions

A team of researchers at MIT has come up with a promising approach to controlling methane emissions and removing it from the air, using an inexpensive and abundant type of clay called zeolite. In this image, the zeolite, depicted as the complex structure in the middle, absorbs the methane that passes through it.
Credits:Image: Darius Siwek

Methane is a far more potent greenhouse gas than carbon dioxide, and it has a pronounced effect within first two decades of its presence in the atmosphere. In the recent international climate negotiations in Glasgow, abatement of methane emissions was identified as a major priority in attempts to curb global climate change quickly.

Now, a team of researchers at MIT has come up with a promising approach to controlling methane emissions and removing it from the air, using an inexpensive and abundant type of clay called zeolite. The findings are described in the journal ACS Environment Au, in a paper by doctoral student Rebecca Brenneis, Associate Professor Desiree Plata, and two others.

Although many people associate atmospheric methane with drilling and fracking for oil and natural gas, those sources only account for about 18 percent of global methane emissions, Plata says. The vast majority of emitted methane comes from such sources as slash-and-burn agriculture, dairy farming, coal and ore mining, wetlands, and melting permafrost. “A lot of the methane that comes into the atmosphere is from distributed and diffuse sources, so we started to think about how you could take that out of the atmosphere,” she says.

T cells from common colds cross-protect against infection with SARS-CoV-2

People with higher levels of T cells from common cold coronaviruses are less likely to become infected with SARS-CoV-2.

A new study, published in Nature Communications and led by Imperial College London researchers, provides the first evidence of a protective role for these T cells. While previous studies have shown that T cells induced by other coronaviruses can recognize SARS-CoV-2, the new study examines for the first time how the presence of these T cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected.

The researchers also say their findings provide a blueprint for a second-generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron.

Dr Rhia Kundu, first author of the study, from Imperial’s National Heart & Lung Institute, says: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.

"Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why." Dr Rhia Kundu National Heart & Lung Institute

"While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone. Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”

The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2. It included 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection and who had therefore been exposed to the virus. The participants did PCR tests at the outset and 4 and 7 days later, to determine if they developed an infection.

80 percent of the skin replaced

After his treatment, the boy was able to do normal work again.
Credit: Catholic Clinic Bochum

New skin from genetically modified stem cells had never been used on such a large area. The patient is stable five years later.

The case is considered unique worldwide: in 2015, a German-Italian team replaced 80 percent of its skin with its genetically modified stem cells for a boy who was then seven years old. He suffered from the life-threatening butterfly disease Epidermolysis bullosa. Those affected have extremely thin skin, which blows, tears and dissolves even with minimal external influences. Around five years later, the skin is stable and has the same sensory qualities as healthy skin. The treatments from the Center for Regenerative Medicine at the University of Módena (Italy) and the Fire Injury Center of the Ruhr University Bochum (RUB) report in the magazine New England Journal of Medicine from 9. December 2021.

The skin is stable, the immune system intact

After all conservative and surgical therapy attempts were unsuccessful at the time, the international team, the small patient, succeeded Remove skin, process it genetically and then transplant it to the wound surfaces This method had never been used on such a large skin area.

Childhood vaccination: the benefits spread beyond children

Professor Michael Good from the Institute for Glycomics, Griffith University

An Australian and Canadian study has found while childhood COVID vaccination leads to high relative reductions in child disease and mortality, it is more beneficial to adults, particularly the unvaccinated.

Accepted into mBio, but available currently on MedRxiv, the research uses a mathematical epidemiological model to forecast the effect of childhood vaccination on the number of COVID-19 cases, hospitalizations, deaths, complications, and vaccine adverse effects in both children and in adults.

“Our model showed that childhood vaccination carries minimal risk, yet can result in large relative reductions in the disease” said Professor Michael Good from the Institute for Glycomics, Griffith University.

Professor Michael Good from the Institute for Glycomics, Griffith University

“For children between 5-11 years of age while we will see a high percent reduction in hospitalizations and deaths, there will not be a huge reduction in the actual number of children being hospitalized or dying because these events were so rare in the first place, even in unvaccinated children.”

The study showed that the biggest benefit of childhood vaccination will, perhaps surprisingly, be seen in adult populations.

“A critical point is that for children aged 5-11 cases of vaccine-associated myocarditis and anaphylaxis are predicted to be very rare, so childhood vaccination can be used altruistically to work for the greater population,” said Professor Michael Hawkes, School of Public Health, University of Alberta.

Circumbinary Planet Discovered by TESS Validates New Detection Technique

The newly discovered planet, TIC 172900988b, is roughly the radius of Jupiter, and several times more massive, but it orbits its two stars in less than one year. This world is hot and unlike anything in our Solar System. 
Credit: PSI/Pamela L. Gay.

A new technique developed in part by Planetary Science Institute Senior Scientist Nader Haghighipour has allowed astronomers to quickly detect a transiting circumbinary planet orbiting around two suns, according to a new Astronomical Journal paper on which Haghighipour is an author.

Circumbinary planets are planetary bodies that rotate around two stars. Although for years, they were merely a matter of science fiction, thanks to the successful operation of NASA’s Kepler and Transiting Exoplanet Survey Satellite (TESS) telescopes, an all-sky survey mission designed to discover thousands of exoplanets around nearby bright stars, a team of astronomers, including Haghighipour, have detected 14 such bodies.

“Detecting circumbinary planets is much more complicated than detecting planets orbiting single stars. The most promising technique for detecting circumbinary planets is transit photometry, which measures drops in starlight caused by those planets whose orbits are oriented in space such that they periodically pass between their stars and the telescope. In this technique, the measurements of the decrease in the intensity of the light of a star is used to infer the existence of a planet,” Haghighipour said. “To determine the orbit of the planet, precisely, at least three transit events are required. This becomes complicated when a planet orbits a double-star system because transits will not happen with the same interval over the same star. The planet may transit one star and then transit the other before transiting the first star again, and so on.”

Anxiety and PTSD linked to increased myelin in brain

A series of fMRI scans of the brain of a military veteran with PTSD, showing gray matter regions with increased myelin. 
Credit: UCSF image by Linda Chao

A recent study links anxiety behavior in rats, as well as post traumatic stress disorder (PTSD) in military veterans, to increased myelin — a substance that expedites communication between neurons — in areas of the brain associated with emotions and memory.

The results, reported by scientists at the University of California, Berkeley, and UC San Francisco (UCSF), provide a possible explanation for why some people are resilient and others vulnerable to traumatic stress, and for the varied symptoms — avoidance behavior, anxiety and fear, for example — triggered by the memory of such stress.

If, as the researchers suspect, extreme trauma causes the increased myelination, the findings could lead to treatments — drugs or behavioral interventions — that prevent or reverse the myelin production and lessen the aftereffects of extreme trauma.

Myelin is a layer of fatty substances and proteins that wraps around the axons of neurons — essentially, the insulation around the brain’s wiring — to facilitate long-distance transmission of signals and, thus, communication between distant areas of the brain. The inner regions of the brain look white — in fact, they are referred to as “white matter” — because of the myelin encasing the many large bundles of axons there.

Dog brains can distinguish between languages

Credit: Photo: Eniko Kubinyi

"Some years ago I moved from Mexico to Hungary to join the Neuroethology of Communication Lab at the Department of Ethology, Eötvös Loránd University for my postdoctoral research. My dog, Kun-kun, came with me. Before, I had only talked to him in Spanish. So I was wondering whether Kun-kun noticed that people in Budapest spoke a different language, Hungarian.” — says Laura V. Cuaya, first author of the study. “We know that people, even preverbal human infants, notice the difference. But maybe dogs do not bother. After all, we never draw our dogs' attention to how a specific language sounds. We designed a brain imaging study to find this out.

Kun-kun and 17 other dogs were trained to lay motionless in a brain scanner, where we played them speech excerpts of The Little Prince in Spanish and Hungarian. All dogs had heard only one of the two languages from their owners, so this way we could compare a highly familiar language to a completely unfamiliar one. We also played dogs scrambled versions of these excerpts, which sound completely unnatural, to test whether they detect the difference between speech and non-speech at all.”

When comparing brain responses to speech and non-speech, researchers found distinct activity patterns in dogs’ primary auditory cortex. This distinction was there independently from whether the stimuli originated from the familiar or the unfamiliar language. There was, however, no evidence that dog brains would have a neural preference for speech over non-speech.

"Dog brains, like human brains, can distinguish between speech and non-speech.

New way to alter DNA, affect health circumvents gut bacteria

John Denu

Our gut microbiome helps us out every day by processing the fiber we can’t digest. The bacteria ferment the fiber into key chemicals known as short-chain fatty acids, or SCFAs, that are essential for human health. SCFAs fight inflammation, help kill dangerous bacteria, protect the lining of the gut, and can even help prevent cancer.

In a new study, the John Denu lab at the University of Wisconsin–Madison’s Wisconsin Institute for Discovery has learned that the fatty acids butyrate and propionate also activate p300, a crucial human enzyme that promotes the unspooling of DNA. This unwound DNA allows more genes to become active and expressed, which ultimately affects human health.

Previous research had suggested that SCFAs might instead contribute to this process by inhibiting a different set of enzymes.

This new understanding opens the possibility of activating p300 in a diet-dependent way or even independently of the microbiome. Knowing how to target p300 is vital because it is implicated in a wide variety of physiological processes and diseases, such as propionic acidemia, autism spectrum disorder, and Alzheimer’s disease.

Sydney Thomas

“Knowing that butyrate and propionate directly interact with this protein opens up a lot of new areas of research that we didn’t even think to look at before, because we thought that it was happening the opposite way than it actually is,” says Sydney Thomas, a Denu lab graduate student and co-author on the paper.

Thomas and Denu, a professor of biomolecular chemistry, published their findings in the journal eLife.

Earlier work in mice had shown that SCFAs are a crucial link between the microbiome and epigenetic states — the modifications to DNA that affect how active any given gene is. These epigenetic modifications allow different cells to use the same DNA instructions to perform different tasks and can affect health.

Cystic Fibrosis Drugs Can Be ‘Life-Changing’ For Patients

Small molecule drugs (outlined in green) nestle in a cavity in the protein that malfunctions in cystic fibrosis, stabilizing the protein and correcting its flaws.
Credit: K. Fiedorczuk et al./ Cell 2022

Just over a decade ago, in one of the great advances in modern medicine, researchers at Aurora Biosciences and then Vertex Pharmaceuticals found what they described at the time as needles in a haystack – small molecule drugs that can treat cystic fibrosis, the lung-damaging genetic disease.

Vertex’s first drug, ivacaftor, was approved in 2012, and others followed, dramatically increasing survival age and quality of life for cystic fibrosis patients. The drugs improve lung function, allowing patients to breathe better. Scientists knew that the drugs somehow adjusted or corrected the faulty protein responsible for the disease, but how they work has remained unknown.

Now, in new work that reveals the structure of the mutated protein and how so-called corrector drugs interact with it, Howard Hughes Medical Institute Investigator Jue Chen’s team at the Rockefeller University has discovered how the molecules operate. They bind to and stabilize the defective protein during its biogenesis, giving it a better chance to successfully reach the cell surface, her team reports January 6, 2022, in the journal Cell.