HIV-1 virus particles under electron micrograph with H9 T-cells (in blue) – Credit: National Institute of Allergy and Infectious Diseases
A new study has unveiled a likely future cure for HIV which uses molecular scissors to ‘cut out’ HIV DNA from infected cells. To cut out this virus, the team used CRISPR-Cas gene editing technology—a groundbreaking method that allows for precise alterations to a patient’s genome, for which its inventors won the Nobel Prize in Chemistry in 2020. One of the significant challenges in HIV treatment is the virus’s ability to integrate its genome into the host’s DNA, making it extremely difficult to eliminate—but the CRISPR-Cas tool provides a new means to isolate and target HIV DNA. Because HIV can infect different types of cells and tissues in the body, each with its own unique environment and characteristics, the researchers are searching for a way to target HIV in all of these situations. In this study, which is to be presented ahead of this year’s European Congress of Clinical Microbiology and Infectious Diseases, the authors used CRISPR-Cas and two guide RNAs against “conserved” HIV sequences. They focused on parts of the virus genome that stay the same across all known HIV strains and infected T cells. Their experiments showed outstanding antiviral performance, managing to completely inactivate HIV with a single guide RNA and cut out the viral DNA with two guide RNAs. “We have developed an efficient combinatorial CRISPR-attack on the HIV virus in various cells and the locations where it can be hidden in reservoirs, and demonstrated that therapeutics can be specifically delivered to the cells of interest,” said Associate professor Elena Herrera Carrillo from the University of Amsterdam AMC. “These findings
HIV AIDS virus (in yellow) infecting a human cell – Credit: National Cancer Institute
represent a pivotal advancement towards designing a cure strategy.” The team has a long way to go before their cure will be available to patients, but said, “These preliminary findings are very encouraging’. Currently, HIV can be kept in check with anti-retroviral medication, but no one has actually been cured—although three patients receiving stem cell transplants for blood cancer were subsequently declared free of the disease when their HIV became undetectable. “We hope to achieve the right balance between efficacy and safety of this CURE strategy,” said Dr. Carrillo. “Only then can we consider clinical trials of ‘cure’ in humans to disable the HIV reservoir.“Our aim is to develop a robust and safe combinatorial CRISPR-Cas regimen, striving for an inclusive ‘HIV cure for all’ that can inactivate diverse HIV strains across various cellular contexts. Scientists Discover Potential HIV Cure that Eliminates Disease from Cells Using CRISPR-Cas Gene Editing
Zebra finches are highly social birds and will press a lever in order to hear a recording of another Zebra finch singing. (Photo by Carlos Rodríguez-Saltos)
By Carol Clark: Oxytocin, the so-called “love hormone,” plays a key role in the process of how a young zebra finch learns to sing by imitating its elders, suggests a new study by neuroscientists at Emory University. Scientific Reports published the findings, which add to the understanding of the neurochemistry of social learning. “We found that the oxytocin system is involved from an early age in male zebra finches learning song,” says Natalie Pilgeram, first author of the study and an Emory PhD candidate in psychology. “It’s basic science that may lead to insights into the process of vocal learning across the animal kingdom, including humans.” “Our results suggest that the neurochemistry of early social bonds, particularly during language learning, may be relevant in studies of autism,” adds Donna Maney, a professor of neuroscience in Emory’s Department of Psychology and senior author of the study. Young male zebra finches learn to sing by listening to an adult male tutor that they choose to pay close attention to, normally their biological father or a “foster” father who nurtures them. This social process holds some similarities for how children learn to speak, making the birds a laboratory model for the neural underpinnings of social vocal learning. In the current paper, the researchers show how oxytocin, a hormone essential to social bonding, influences young finches exposed only to the songs of unfamiliar males. In experiments, blocking the young birds’ oxytocin receptors while they listened to a male biased the birds against that male’s song. Instead they preferred to listen to and eventually learn the song of a male they heard when their oxytocin receptors were allowed to function normally. The paper builds on previous work by the Maney lab regarding the hormonal and genetic influences on social behavior. Her lab is working with researchers at the Marcus Autism Center in Atlanta to maximize any potential translational impact of its research findings. Finding their voice: Zebra finches are highly social birds. In the wild they nest together in large colonies. Only adult males sing, primarily to court females. From the time they hatch, the males begin listening for song, and memorizing particular songs, even before they can actually sing one. “Up until around day 50, they are making little cheeps and warbles, what we call ‘subsong,’” Pilgeram explains. “It’s similar to human infants who begin to babble at around six months without actually talking.” During this sensitive listening phase, a male zebra finch pays closest attention to the song of its father, even though it can hear other adult males nearby. In a laboratory environment, research shows that if a biological father is removed from a cage before a male hatches and then substituted with a “foster father” that they can interact with, the young male will prefer the song of the foster father over other males it can hear. The young males demonstrate this preference by pressing levers that allow them to hear playback of different songs. Learning from their environment: “The young birds have got to learn all that they can from their environment,” Pilgeram says. “Just as during human development, the birds pay the closest attention to their immediate caregivers, on whom they rely for everything.” Around day 50, the young male finches enter puberty and what is called the “plastic song phase.” During this time, they practice their song motor skills and actively try to produce song. Although they begin to shift their attention away from their fathers and show a preference for hearing songs of other males, each young male still practices dad’s tune. By day 100, most male zebra finches are fully singing their father’s song. They have reached adulthood and their tune has “crystalized” into the song that they will sing for the rest of their lives. In previous research, the Maney lab found that the stronger the preference a male zebra finch shows for its father’s song during the early listening phase, the more closely its crystalized adult song will mimic that of the father. The role of oxytocin: For the current paper, the researchers wanted to test whether the oxytocin system played a role in that preference. The research centered on male juvenile zebra finches hatched in the lab. At day four, the fathers were removed from each of the youngsters’ cages so they were raised only by their mothers. The cages were enclosed in chambers that prevented the young birds from hearing song from other birds housed nearby. Beginning at day 27 in a young bird’s life, it was exposed to a series of tutoring sessions by two different adult male tutors that it had never heard. The tutor’s cage was placed next to the cage of the young bird, or pupil. When it was exposed to one of the tutors, the pupil was given a substance that blocked its oxytocin receptors from activating. When the young bird was exposed to the other tutor it received a control substance that allowed its oxytocin receptors to function normally. After completing a series of tutoring sessions, the pupils were presented with two different levers they could press in their cages. Pressing one lever was more likely to play the song they heard when their oxytocin receptors were blocked. The other lever was more likely to play the song they heard with normally functioning oxytocin. The results showed that early in their development, the juveniles favored the song that they heard when their oxytocin was not blocked. Building on past findings: “We also found that when their oxytocin was not blocked, the birds’ developmental milestones fit the same data curve as in our previous research,” Maney says. “They showed an early preference for the song of one tutor, then switched to preferring the other song during puberty.” The preference flattened out as they began singing the song of their chosen tutor, she adds. And the stronger the preference that they showed for the chosen tutor’s song during the early listening phase, the more closely their own adult song resembled that of the chosen tutor. The researchers also noted behavioral differences in the way the pupils and tutors interacted. With normally functioning oxytocin, a pupil pecked more often at the wall of its cage facing the tutor and more often preened in a fashion known to be associated with focused listening in the birds, compared to when its oxytocin was blocked. “Our results suggest that the oxytocin system is involved in how an animal decides where to focus its attention very early in its life,” Pilgeram says. Co-authors of the study include Carlos Rodríguez-Saltos, who received his doctorate from Emory and is now at Illinois State University; postdoctoral fellow Nicole Baran; research technicians Matthew Davis and Erik Iverson; and Emory undergraduates Sumin Lee, Emily Kim and Aditya Bhise. The work was funded by the National Science Foundation and the Silvio O. Conte Center for Oxytocin and Social Cognition. eScienceCommons: 'Love hormone' guides young songbirds in choice of.
Since the first detonation of an atomic bomb in 1945, more than 2,000 nuclear weapons tests have been conducted by eight countries: the United States, the Soviet Union, the United Kingdom, France, China, India, Pakistan and North Korea.
Groups such as the Comprehensive Nuclear-Test-Ban Treaty Organization are constantly on the lookout for new tests. However, for reasons of safety and secrecy, modern nuclear tests are carried out underground – which makes them difficult to detect. Often, the only indication they have occurred is from the seismic waves they generate.
The invention of nuclear weapons sparked an international arms race, as the Soviet Union, the UK and France developed and tested increasingly larger and more sophisticated devices in an attempt to keep up with the US.
Many early tests caused serious environmental and societal damage. For example, the US’s 1954 Castle Bravo test, conducted in secret at Bikini Atoll in the Marshall Islands, delivered large volumes of radioactive fallout to several nearby islands and their inhabitants.
Between 1952 and 1957, the UK conducted several tests in Australia, scattering long-lived radioactive material over wide areas of South Australian bushland, with devastating consequences for local Indigenous communities.
In 1963, the US, the UK and the USSR agreed to carry out future tests underground to limit fallout. Nevertheless, testing continued unabated as China, India, Pakistan and North Korea also entered the fray over the following decades.
How to spot an atom bomb
During this period there were substantial international efforts to figure out how to monitor nuclear testing. The competitive nature of weapons development means much research and testing is conducted in secret.
Groups such as the Comprehensive Nuclear-Test-Ban Treaty Organization today run global networks of instruments specifically designed to identify any potential tests. These include:
air-testing stations to detect minute quantities of radioactive elements in the atmosphere
aquatic listening posts to hear underwater tests
infrasound detectors to catch the low-frequency booms and rumbles of explosions in the atmosphere
seismometers to record the shaking of Earth caused by underground tests.
A needle in a haystack
Seismometers are designed to measure seismic waves: tiny vibrations of the ground surface generated when large amounts of energy are suddenly released underground, such as during earthquakes or nuclear explosions.
There are two main kinds of seismic waves. First are body waves, which travel outwards in all directions, including down into the deep Earth, before returning to the surface. Second are surface waves, which travel along Earth’s surface like ripples spreading out on a pond.
The Comprehensive Test-Ban-Treaty Organization uses seismic stations to monitor the globe for underground nuclear explosions.
The difficulty in using seismic waves to monitor underground nuclear tests is distinguishing between explosions and naturally occurring earthquakes. A core goal of monitoring is never to miss an explosion, but there are thousands of sizeable natural quakes around the world every day.
As a result, monitoring underground tests is like searching for a potentially non-existent needle in a haystack the size of a planet.
Nukes vs quakes
Many different methods have been developed to aid this search over the past 60 years.
Some of the simplest include analysing the location or depth of the source. If an event occurs far from volcanoes and plate tectonic boundaries, it might be considered more suspicious. Alternatively, if it occurs at a depth greater than say three kilometres, it is unlikely to have been a nuclear test.
However, these simple methods are not foolproof. Tests might be carried out in earthquake-prone areas for camouflage, for example, and shallow earthquakes are also possible.
A more sophisticated monitoring approach involves calculating the ratio of the amount of the energy transmitted in body waves to the amount carried in surface waves. Earthquakes tend to expend more of their energy in surface waves than explosions do.
This method has proven highly effective for identifying underground nuclear tests, but it too is imperfect. It failed to effectively classify the 2017 North Korean nuclear test, which generated substantial surface waves because it was carried out inside a tunnel in a mountain.
This outcome underlines the importance of using multiple independent discrimination techniques during monitoring – no single method is likely to prove reliable for all events.
An alternative method
In 2023, my colleagues and I from the Australian National University and Los Alamos National Laboratory in the US got together to re-examine the problem of determining the source of seismic waves.
We used a recently developed approach to represent how rocks are displaced at the source of a seismic event, and combined it with a more advanced statistical model to describe different types of event. As a result, we were able to take advantage of fundamental differences between the sources of explosions and earthquakes to develop an improved method of classifying these events.
We tested our approach on catalogues of known explosions and earthquakes from the western United States, and found that the method gets it right around 99% of the time. This makes it a useful new tool in efforts to monitor underground nuclear tests.
Robust techniques for identification of nuclear tests will continue to be a key component of global monitoring programs. They are critical for ensuring governments are held accountable for the environmental and societal impacts of nuclear weapons testing.
HIV-1 virus particles under electron micrograph with H9 T-cells (in blue) – Credit: National Institute of Allergy and Infectious Diseases
