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Engadget’s resident laptop expert Devindra Hardawar put the . Fundamentally, both are fantastic machines but probably lack some of the gosh-wow factor the M2 Airs had when they debuted in 2022. After all, the M2 heralded a new industrial design and far better internals, while the M3 is more of an iterative update. Think of it like the iPhone S-years, when a dramatic redesign (the iPhone 4, say) was followed by a more refined model (the 4S) the following year.
Consequently, reviewing the M3 is an exercise in spotting the small differences, like the faster Wi-Fi (6E), brighter display and quicker processing speed. Benchmarking saw both machines get out ahead of the M2, but you probably won’t notice if you’re using this machine casually. And Devindra’s clearly getting a kick out of being able to run games like Death Stranding on a fanless ultraportable. You can — and should — read on to find out if the M3 is a must-buy.
— Dan Cooper
The biggest stories you might have missed
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It’s great for video, less ideal for everything else.
Steve Dent for Engadget
Steve Dent, who knows more about cameras than I know about literally anything, has been using . He’s never been too much of a fan of Sony’s 6000-series models, which he says aren’t as good looking or usable as Fujifilm’s alternatives. The A6700 is an attempt to remedy this situation, and Steve says it’s a far better camera than its predecessor. But is it good enough for him to want to use it as his daily driver? You’ll have to read on to find out.
Can the US Government withstand the stan army?
The geopolitical quagmire surrounding TikTok isn’t letting up, which has led the platform to use its secret weapon: its Stan Army. . It’s one way to get attention, but it may not endear the company to US lawmakers if it can so easily incite millions of people to start scrutinizing the political process all at once.
And the loser will probably be… humanity itself.
Netflix is devolving into the very thing it sought to destroy. It’s been stepping into the live broadcast space for a while and yesterday announced it . Given the high-profile nature of the participants and, presumably, people’s desire to see one or both get punched in the face, it should be a massive event. And it’s going to be the sternest test of Netflix’s capacity to use the internet to deliver millions of simultaneous streams of live TV.
It upended the EV world in so many ways, at least at the time.
Koren Shadmi for Engadget
Engadget is celebrating its 20th anniversary with a series of articles looking back on the biggest changes in the tech world over that time. The wonderful Tim Stevens is in the spotlight today to talk about the . It’s a tale of the car’s innovations, its highs, lows and how the EV industry has changed in the ensuing years.
The James Webb Space Telescope makes one of the most unexpected findings within its first year of service: A high number of faint little red dots in the distant Universe could change the way we understand the genesis of supermassive black holes. The research, led by Jorryt Matthee, Assistant Professor in astrophysics at the Institute of Science and Technology Austria (ISTA), is now published in The Astrophysical Journal.
A bunch of little red dots found in a tiny region of our night sky might be an unexpected breakthrough for the James Webb Space Telescope (JWST) within its first year of service. These objects were indistinguishable from normal galaxies through the ‘eyes’ of the older Hubble Space Telescope. “Without having been developed for this specific purpose, the JWST helped us determine that faint little red dots-found very far away in the Universe’s distant past-are small versions of extremely massive black holes. These special objects could change the way we think about the genesis of black holes,” says Jorryt Matthee, Assistant Professor at the Institute of Science and Technology Austria (ISTA), and lead author of the study. “The present findings could bring us one step closer to answering one of the greatest dilemmas in astronomy: According to the current models, some supermassive black holes in the early Universe have simply grown ‘too fast’. Then how did they form?”
The cosmic points of no return
Scientists have long considered black holes a mathematical curiosity until their existence became increasingly evident. These strange cosmic bottomless pits could have such compact masses and strong gravities that nothing can escape their force of attraction-they suck in anything, including cosmic dust, planets, and stars, and deform the space and time around them such that even light cannot escape. The general theory of relativity, published by Albert Einstein over a century ago, predicted that black holes could have any mass. Some of the most intriguing black holes are the supermassive black holes (SMBHs), which could reach millions to billions of times the mass of the Sun. Astrophysicists agree that there is an SMBH at the center of almost every large galaxy. The proof that Sagittarius A* is an SMBH in the center of our Galaxy with over four million times the Sun’s mass, earned the 2020 Nobel Prize in Physics.
Too massive to be there
However, not all SMBHs are the same. While Sagittarius A* could be compared to a sleeping volcano, some SMBHs grow extremely rapidly by engulfing astronomic amounts of matter. Thus, they become so luminous that they can be observed until the edge of the ever-expanding Universe. These SMBHs are called quasars and are among the brightest objects in the Universe. “One issue with quasars is that some of them seem to be overly massive, too massive given the age of the Universe at which the quasars are observed. We call them the ‘problematic quasars,'” says Matthee. “If we consider that quasars originate from the explosions of massive stars-and that we know their maximum growth rate from the general laws of physics, some of them look like they have grown faster than is possible. It’s like looking at a five-year-old child that is two meters tall. Something doesn’t add up,” he explains. Could SMBHs perhaps grow even faster than we originally thought? Or do they form differently?
Small versions of giant cosmic monsters
Now, Matthee and his colleagues identify a population of objects that appear as little red dots in JWST images. Also, they demonstrate that these objects are SMBHs, but not overly massive ones. Central in determining that these objects are SMBHs was the detection of Hα spectral emission lines with wide line profiles. Hα lines are spectral lines in the deep-red region of visible light that are emitted when hydrogen atoms are heated. The width of the spectra traces the motion of the gas. “The wider the base of the Hα lines, the higher the gas velocity. Thus, these spectra tell us that we are looking at a very small gas cloud that moves extremely rapidly and orbits something very massive like an SMBH,” says Matthee. However, the little red dots are not the giant cosmic monsters found in overly massive SMBHs. “While the ‘problematic quasars’ are blue, extremely bright, and reach billions of times the mass of the Sun, the little red dots are more like ‘baby quasars.’ Their masses lie between ten and a hundred million solar masses. Also, they appear red because they are dusty. The dust obscures the black holes and reddens the colors,” says Matthee. But eventually, the outflow of gas from the black holes will puncture the dust cocoon, and giants will evolve from these little red dots. Thus, the ISTA astrophysicist and his team suggest that the little red dots are small, red versions of giant blue SMBHs in the phase that predates the problematic quasars. “Studying baby versions of the overly massive SMBHs in more detail will allow us to better understand how problematic quasars come to exist.”
A “breakthrough” technology
Matthee and his team could find the baby quasars thanks to the datasets acquired by the EIGER (Emission-line galaxies and Intergalactic Gas in the Epoch of Reionization) and FRESCO (First Reionization Epoch Spectroscopically Complete Observations) collaborations. These are a large and a medium JWST program in which Matthee was involved. Last December, the Physics World magazine listed EIGER among the top 10 breakthroughs of the year for 2023. “EIGER was designed to study specifically the rare blue supermassive quasars and their environments. It was not designed to find the little red dots. But we found them by chance in the same dataset. This is because, by using the JWST’s Near Infrared Camera, EIGER acquires emission spectra of all objects in the Universe,” says Matthee. “If you raise your index finger and extend your arm completely, the region of the night sky we explored corresponds to roughly a twentieth of the surface of your nail. So far, we have probably only scratched the surface.”
Matthee is confident that the present study will open up many avenues and help answer some of the big questions about the Universe. “Black holes and SMBHs are possibly the most interesting things in the Universe. It’s hard to explain why they are there, but they are there. We hope that this work will help us lift one of the biggest veils of mystery about the Universe,” he concludes.
Andrew Day, a molecular microbiologist at Tufts University in Medford, Massachusetts, is four years sober. His journey to this point inspires his work, which he hopes might help others who are struggling with alcohol.
Nature Outlook: The human microbiome
There are many risk factors associated with alcohol-use disorder (AUD), including mental-health conditions and genetics. But Day is eyeing a more unusual contributor: the gut.
Over the past decade, research has begun to highlight a link between the gastrointestinal microbiome — the microorganisms that live inside our digestive tract — and addiction. Researchers including Day suggest that an imbalance in the intestinal microbiota, known as dysbiosis, might cause the gut to send signals to the brain that promote addiction behaviours. If correct, the gut could become a treatment target for people with AUD. “I could find something that might make it easier for people who might not be as fortunate to maintain sobriety,” says Day, who is studying the theory that high levels of the fungus Candida albicans in the gut contributes to increased alcohol consumption in mice as part of his PhD.
This is a sharp departure from conventional medical approaches to treating addiction. Most drugs for AUD and substance-use disorder (SUD) focus on brain chemistry. Many of them are not very effective. Medications for AUD approved by the US Food and Drug Administration (FDA) include naltrexone and acamprosate. In addition, the European Medicines Agency (EMA) has approved nalmefene. Acamprosate modulates brain receptors such as those that bind γ-aminobutyric acid (GABA), an inhibitory neurotransmitter thought to have a role in withdrawal, craving and impulsive behaviour. Nalmefene and naltrexone modulate opioid receptors, nalmefene reduces alcohol cravings, and naltrexone blocks euphoric sensations associated with alcohol.
According to the US Substance Abuse and Mental Health Services Administration, only 42% of people who receive treatment for any kind of SUD complete that treatment1. Between 40% and 60% of people with an SUD will relapse, and it can take years — sometimes decades — of see-sawing between abstinence and relapse before someone achieves sustained remission. Clearly, there is room for improvement. “We’ve missed the target for 50 years,” says Benjamin Boutrel, a neurobiologist at Lausanne University Hospital in Switzerland. “Mostly because it’s not only a matter of the brain — it’s possibly a matter of the guts, too.”
The gut–brain axis
It is now well known that there is complex communication between the gut and the brain, through the vagus nerve as well as through the endocrine and immune systems. This gut–brain signalling has been suggested to influence addiction-related behaviours in two main ways.
Andrew Day hopes his research will help others who have alcohol-use disorder.Credit: Dr. Carol Kumamoto
The first involves a condition known as leaky gut. Stress, poor diet, food allergies, chemotherapy and other medication, conditions such as inflammatory bowel disease and — perhaps crucially — overuse of alcohol can damage the layer of epithelial cells that line the intestines. This can make the intestinal wall permeable to food particles and bacteria, which can then sneak into the circulatory system.
When this happens, immune cells secrete inflammatory mediators such as cytokines. These proteins can then reach the brain, either through the vagus nerve or by crossing weak areas in the blood–brain barrier, a layer of cells meant to protect the brain from damage.
The subsequent inflammation can affect the brain in several ways that could promote addiction. Cytokines deplete tryptophan, which can lead to reduced production of the mood-regulating hormone serotonin. The brain’s amygdala might sense a threat in the body and increase its activity in response to inflammation. The ventral striatum — the area of the brain related to reward anticipation — might also be ignited. The anterior cingulate cortex — the part of the brain involved in inhibitory control and compulsive behaviour — can also activate during inflammation.
Second, the molecules that gut microbes produce could influence addiction. Some of these are important for brain functioning. The gut bacteria Lactobacillus, for example, can produce GABA; Enterococcus can produce serotonin; and Bacillus can make dopamine. Short-chain fatty acids (SCFAs) released when dietary fibre is fermented by bacteria in the gut also have neuroactive properties.
Gut dysbiosis, and its subsequent impact on GABA, serotonin, dopamine and tryptophan, could, therefore, make a person more susceptible to addiction and mean that they experience more severe withdrawal symptoms than would someone with a healthy gut microbiome.
“The gut microbiome is really important for some organs, including the brain,” says Drew Kiraly, a psychiatrist and physician at Wake Forest University in Winston-Salem, North Carolina. Kiraly has observed associations between dysbiosis and addictive behaviour to stimulants and opioids in rats. He has used antibiotics to deplete rats’ beneficial gut microbes, resulting in “aberrant responses to drugs”. The animals had increased intake of cocaine and fentanyl, he says. “And after withdrawal, they relapse and have higher fentanyl-seeking behaviour.”
Addictive personality
Even before first contact with alcohol or drugs, pre-existing dysbiosis could make someone more vulnerable to addiction, Boutrel says. The imbalance could give rise to traits such as impulsivity, boredom, susceptibility to stress or anxiety, and sensation seeking. “Those who get thrilled with poker playing, with pathological sex, they all need something,” Boutrel says. “There is a vulnerability there that, once that first contact is made, will trigger repetition — and finally, addiction.”
Sophie Leclercq is one of few researchers able to study theories about the gut microbiome in people with alcohol-use disorder.Credit: Sophie Leclercq
In 2018, Boutrel and his colleagues put a group of 59 rats through a number of tests designed to assess their vulnerability to AUD2. First, the rodents were trained to self-administer alcohol by pressing a lever. The researchers then tried to gauge the rats’ self-control by introducing a delay to the reward delivery. Some rats pressed the button once, realized that they had to wait, and went about their business. But some would continue pressing over and over, attempting to make the alcohol arrive more quickly — an indication of addiction.
The final test, which Boutrel thinks is most telling, introduced a deterrent — an uncomfortable foot shock every time the animals took the alcohol. For most of the rats, this discouragement was sufficient and they stopped pressing the lever. However, a sizable minority “just didn’t care”, Boutrel says. “They could not stop pressing the lever and accessing the reward, even when they got a punishment.” In total, about 30% of the rats demonstrated vulnerability to AUD.
Having identified a group of vulnerable rats, Boutrel and his colleagues removed alcohol from the rats environment for three months, and then compared the brains and gut microbiomes of the vulnerable rats with those of rats that had proven more resistant to AUD. The team found that the vulnerable rats had more efficient dopamine 1 receptors (which trigger increased reward-seeking and motivation) and less efficient dopamine 2 receptors (which cause impulsivity, and an increased need for immediate rewards and drug administration). They also found differences in the bacterial content of the vulnerable-rat guts — most notably, changes in Lachnospiraceae, Syntrophococcus and other bacteria associated with reductions in dopamine 2 receptors. This, the researchers suggest, is an indication that gut microbiota could affect brain circuits associated with addiction.
Alcohol and other drugs
Sophie Leclercq, a biomedical scientist at the Catholic University of Louvain in Brussels, was an early advocate of the theory about an AUD gut–brain origin, and one of the first to test it in people3. Her aim was to find out whether intestinal permeability was related to character traits that might make people more susceptible to alcohol dependence.
Lactobacillus gut bacteria can produce the inhibitory neurotransmitter GABA.Credit: BSIP/UIG Via Getty Images
Leclercq and her colleagues tested the intestinal permeability of 60 people with AUD two days after they began withdrawal. The researchers found that 26 (43%) had high intestinal permeability. At the beginning of the study, everyone with AUD had higher scores of depression, anxiety and craving than did people in the control group. At the end of three weeks of abstinence, the scores of people with low intestinal permeability returned to levels equal to those of the control group. People with high intestinal permeability, however, still scored highly in tests of depression, anxiety and craving, which are directly related to the urge to drink and have a major role in whether people can abstain after detoxification.
“We wanted to see if there was some connection between the gut microbiota and the psychology of AUD, and, indeed, we found that there is a very strong association between dysbiosis, the alteration of the gut microbiota composition, and symptoms like depression, anxiety or grief,” Leclercq says.
Although much of this research is related to people with AUD, Kiraly says that they’ve seen similar results in people who misuse opioids, and cocaine and other stimulants. “Depletion [of microbiota] seems to dysregulate these networks that underlie behavioural changes,” he says.
In 2023, Kiraly and his colleagues looked at whether rats’ microbiomes affected the animal’s drug-seeking behaviours4. In one experiment, rats were given either clean water or water containing the antibiotics neomycin, vancomycin, bacitracin and pimaricin, all of which would deplete their gut microbiota. They were then let into a chamber in which they could push a lever that lit up and provided 0.8 milligrams of cocaine. Later, researchers altered how the lever behaved — now it would light up when pushed, but would have to be pushed more times for the rats to receive cocaine. Researchers found that the rats with depleted gut microbiota were much more likely to press the lever repeatedly to receive cocaine than were the rats given only water.
In a second experiment, both groups of rats were able to self-administer cocaine for two weeks, then detoxed for 21 days. When the rats returned to the cages in which cocaine was available, those receiving antibiotics headed to the lever that originally dosed cocaine twice as quickly as the other rats did. These rats also pressed the lever much more frequently than the control rats did.
“We wanted to study a model of relapse and we saw that microbiome-depleted animals work harder for a drug-related cue than the others did,” Kiraly said. “Lots of people use drugs and not all get to the stage of problematic use. It could be that your microbiome predisposes you.”
Treatment questions
There is still a lot of research that needs to be done before any microbiome-targeted treatment could be offered to people with AUD or another SUD. Researchers don’t yet know, for example, which microbiota are most important, and which gut–brain pathways they need to target. “People have asked me, ‘Can someone just eat yogurt and cure their addiction?’” Kiraly says. “It’s going to be much, much more complicated than that.”
Kiraly would like to see whether probiotics or other treatments could have potential for people with early problematic use but who have not yet progressed to AUD. For instance, some rats in Kiraly’s study were administered SCFAs alongside their antibiotics. Compared with rats that received only antibiotics, those also given SCFAs seemed to retain more Firmicutes and less Proteobacteria (many of which are pathogenic). Strikingly, when the post-detox rats were given the chance to consume cocaine again, those who had received SCFAs behaved like rats with normal gut flora.
Leclercq thinks that 30–40% of cases of AUD might have a gut-related component that could be targeted for treatment. A key challenge is determining exactly which components to target — it is as yet unclear what constitutes a ‘good’ microbiome. Day’s analysis suggests that bacteria such as Lactobacillus, were in abundance in people with AUD, whereas Akkermansia and some others were low.
There is also uncertainty regarding what would be the most effective and easiest part to target of the chain of communication between the gut and brain. Areas such as the nervous system, blood stream or the system surrounding the gut are all candidates.
It is also tricky to find people with AUD who are willing to not only abstain from drinking, but also take part in research, including providing samples of their gut microbiome. Leclercq is one of few researchers able to work with people, instead of rats, because she is affiliated with a hospital with a detoxification clinic. But even she can find it difficult to get enough volunteers for studies. In work assessing the effects of a prebiotic on people with AUD, the number of people with dysbiosis was around half that of those who had healthy guts, making comparisons between the two difficult. Leclercq’s analysis of this aspect of the study is yet to be published.
Despite these issues, Leclercq is moving forward with her research, and is now looking at nutrition as a way to improve the gut microbiome. She is starting a study on polyunsaturated fatty acids — such as those abundant in rapeseed and maize (corn) oils, walnuts, tofu and fatty fish, including salmon and mackerel — and hopes to have results in about two years. She’s also working to correlate which metabolites from food are related to depression, anxiety and craving, and trying to find funding for a study to test these particular nutritional compounds in people.
“Pharmaceutical companies have tried to target GABA, dopamine and serotonin, and these treatments aren’t very efficient because the relapse rate is very high in this disease,” she says. For people with AUD whose guts are contributing to their condition, nutritional interventions, probiotics and prebiotics could eventually improve the odds of success.
Ever compared Cassidy to Spike Siegel or gunslinger Ashe to gun-toting Faye Valentine? Write this date down: March 12. That’s when Blizzard is launching Overwatch 2’s collaboration with legendary anime Cowboy Bebop, which will bring five skins based on the show to the game. The trailer released for the collaboration also shows the hacker Sombra dressed as her fellow hacker Ed, the Tank hero Wrecking Ball/Hammond as the data corgi Ein and the Samoan warrior Mauga as Jet Black.
Speaking of that trailer, it certainly looks and feels like Cowboy Bebop’s opening animation — it even uses the same theme song. Clearly, this collaboration is looking to appeal to the anime’s fans, though we wish it could’ve happened sooner, say during the show’s 25th anniversary last year. Blizzard did launch an anime tie-up in 2023, but it was with Japanese superhero show One-Punch Man.
Wrecking Ball’s Ein skin will be available for free to all players, but the other skins will be sold through the Overwatch 2 shop. The collaboration will also give you access to new emotes, highlight intros and other items you can buy. Blizzard will officially introduce each skin and item on March 11, perhaps so you’d at least have an idea of how much you’re spending a day later.
Dell has launched a massive month-long sale featuring terrific deals across a variety of laptops, PCs, monitors and other computing hardware. Given we rate Dell devices such as the Inspiron and XPS lineup as some of the best laptops you can buy, I’ve focused on those here and picked out six of the best laptop deals available in the Dell TechFest sale.
• Browse the full Dell TechFest sale
For a cheap and excellent value-for-money option, don’t pass up on this Dell Inspiron 15 for $279.99. It’s a relatively basic 15-inch laptop but it’s built with light use and general everyday tasks in mind such as web browsing, sending emails, video calls, word processing, and video streaming. We’re impressed that it comes with 8GB of RAM for a decent performance boost and a chunky 512GB SSD. Large speedy storage options like this are rarely seen on laptops this cheap.
If you’ve got a larger budget and need a laptop with a bit more juice or for more advanced tasks, then consider this Dell XPS 13 Plus for $999.99. This is a fantastic record-low price for a powerful, portable, and stylish machine that can comfortably handle all of your computing needs.
You can see both of these deals and more of the best offers from the Dell TechFest sale below. Remember, you can also check out all the latest Dell coupon codes for ways to save even more money at the manufacturer.
A research team led by Professor Yuanliang ZHAI at the School of Biological Sciences, The University of Hong Kong (HKU) collaborating with Professor Ning GAO and Professor Qing LI from Peking University (PKU), as well as Professor Bik-Kwoon TYE from Cornell University, has recently made a significant breakthrough in understanding how the DNA copying machine helps pass on epigenetic information to maintain gene traits at each cell division. Understanding how this coupled mechanism could lead to new treatments for cancer and other epigenetic diseases by targeting specific changes in gene activity. Their findings have recently been published in Nature.
Background of the Research
Our bodies are composed of many differentiated cell types. Genetic information is stored within our DNA which serves as a blueprint guiding the functions and development of our cells. However, not all parts of our DNA are active at all times. In fact, every cell type in our body contains the same DNA, but only specific portions are active, leading to distinct cellular functions. For example, identical twins share nearly identical genetic material but exhibit variations in physical characteristics, behaviours and disease susceptibility due to the influence of epigenetics. Epigenetics functions as a set of molecular switches that can turn genes on or off without altering the DNA sequence. These switches are influenced by various environmental factors, such as nutrition, stress, lifestyle, and environmental exposures.
In our cells, DNA is organised into chromatin. The nucleosome forms a fundamental repeating unit of chromatin. Each nucleosome consists of approximately 147 base pairs of DNA wrapped around a histone octamer which is composed of two H2A-H2B dimers and one H3-H4 tetramer. During DNA replication, parental nucleosomes carrying the epigenetic tags, also known as histone modifications, are dismantled and recycled, ensuring the accurate transfer of epigenetic information to new cells during cell division. Errors in this process can alter the epigenetic landscape, gene expression and cell identity, with potential implications for cancer and ageing. Despite extensive research, the molecular mechanism by which epigenetic information is passed down through the DNA copying machine, called the replisome, remains unclear. This knowledge gap is primarily due to the absence of detailed structures that capture the replisome in action when transferring parental histones with epigenetic tags. Studying the process is challenging because of the fast-paced nature of chromatin replication, as it involves rapid disruption and restoration of nucleosomes to keep up with the swift DNA synthesis.
In previous studies, the research team made significant progress in understanding the DNA copying mechanism, including determining the structures of various replication complexes. These findings laid a solid foundation for the current research on the dynamic process of chromatin duplication.
Summary of Research Findings
This time, the team achieved another breakthrough by successfully capturing a key snapshot of parental histone transfer at the replication fork. They purified endogenous replisome complexes from early-S-phase yeast cells on a large scale and utilised cryo-electron microscopy (cryo-EM) for visualisation.
They found that a chaperone complex FACT (consisting of Spt16 and Pob3) interacts with parental histones at the front of the replisome during the replication process. Notably, they observed that Spt16, a component of FACT, captures the histones that have been completely stripped off the duplex DNA from the parental nucleosome. The evicted histones are preserved as a hexamer, with one H2A-H2B dimer missing. Another protein that involved in DNA replication, Mcm2, takes the place of the missing H2A-H2B dimer on the vacant site of the parental histones, placing the FACT-histone complex onto the front bumper of the replisome engine, called Tof1. This strategic positioning of histone hexamer on Tof1 by Mcm2 facilitates the subsequent transfer of parental histones to the newly synthesised DNA strands. These findings provide crucial insights into the mechanism that regulates parental histone recycling by the replisome to ensure the faithful propagation of epigenetic information at each cell division.
This study, led by Professor Zhai, involved a collaborative effort that spanned nearly eight years, starting at HKUST and concluding at HKU. He expressed his excitement about the findings, ‘It only took us less than four months from submission to Nature magazine to the acceptance of our manuscript. The results are incredibly beautiful. Our cryo-EM structures offer the first visual glimpse into how the DNA copying machine and FACT collaborate to transfer parental histone at the replication fork during DNA replication. This knowledge is crucial for elucidating how epigenetic information is faithfully maintained and passed on to subsequent generations. But, there is still much to learn. As we venture into uncharted territory, each new development in this field will represent a big step forward for the study of epigenetic inheritance.’
The implications of this research extend beyond understanding epigenetic inheritance. Scientists can now explore gene expression regulation, development, and disease with greater depth. Moreover, this breakthrough opens up possibilities for targeted therapeutic interventions and innovative strategies to modulate epigenetic modifications for cancer treatment. As the scientific community delves deeper into the world of epigenetics, this study represents a major step towards unravelling the complexities of replication-coupled histone recycling.
Megan Majocha, a tumour-biology researcher in the laboratory at the US National Institutes of Health in Bethesda, Maryland, says Deaf researchers shouldn’t have to spend time developing sign language for their science.Credit: NIH
Sign language in science
The lack of scientific terms and vocabulary in many of the world’s sign languages can make science education and research careers inaccessible for deaf people and those with hearing loss. Meet the scientists, sign-language specialists and students working to add scientific terms and concepts to sign languages. In the third of four articles showcasing their efforts, Megan Majocha, a tumour-biology PhD student at Georgetown University in Washington DC, who is part of the Georgetown–National Institutes of Health Graduate Partnerships Program, describes how she worked with interpreters to develop the signed scientific lexicon necessary to conduct her research.
I am from a third-generation Deaf family in Pittsburgh, Pennsylvania. I went to a primary school for Deaf children and then to a mainstream secondary school at the age of 12. My parents thought it would be a good idea for me to learn how to work with interpreters in the mainstream, hearing world while I was at school, so that I had exposure to both worlds.
I worked with the same interpreter for six years from grade 7 (age 12) until the end of secondary school. We collaborated to develop signs for scientific terms — asking each other, “Would this sign make sense for this specific term,” and that kind of thing. It was a lot of work for me in my early teens, to try to develop these scientific signs as well as learning the subject content.
I started my PhD in August 2019 at Georgetown University in Washington DC. I am in my fifth year and I expect to defend my thesis in the next few months. Speaking to a few other Deaf scientists during my PhD, I learnt that we all have different signs for scientific terms: even though they have the same meaning in English, we all sign them differently because we have all developed our own separate ways of signing terms that aren’t in the American Sign Language (ASL) dictionary.
I had to develop my own team of interpreters for my first-year graduate school courses. They worked with me Monday to Friday for each course I took and in the laboratory. It is beneficial to have that consistency for both me and my interpreting team, because we can develop signs together and the interpreters can become familiar with my work and the content of the course for each class.
Adding scientific signs to Indian Sign Language will create a more inclusive field for deaf students
By law, US universities are required to provide and pay for interpreters, so both my institutions, Georgetown University and the US National Institutes of Health (NIH) in Bethesda, Maryland, provide interpreters at no cost to me.
I have to be conscious of how an interpreter might voice my research and scientific ideas to my colleagues, collaborators and prospective mentors. I’d be hesitant to pick an interpreter whom I didn’t know to speak on my behalf, especially for a formal presentation — partly because some scientific terms share the same sign. For example, the signs for the words ‘dye’ and ‘stain’ are the same in ASL — on both hands the index finger and thumb are touching, the other fingers are extended with the palms facing down, and the hands move up and down to represent dipping a material into a dye. Although it’s the same sign, the English words have completely different meanings in the scientific field. If I’m doing a presentation and the interpreter uses the wrong word, that can make me look like I’m not knowledgeable and that I don’t know what I’m talking about.
Having an interpreter who’s motivated to learn these nuances is really important. For example, the interpreters here at the NIH watch the lab team do experiments and ask questions about our research, which is helpful. When I have to stop to explain things, I try not to think of it as wasting my time, when I could be doing my own work. Sometimes I have to take a few minutes to explain a process or concept while I do an experiment, but that can be beneficial in the long run.
Progress and burnout
I’ve focused on developing signs that work for me and my interpreters. But ASL has specific grammar rules for each sign, which a lot of the signs my interpreters and I have created probably don’t follow. That’s one of our many challenges: to develop signs for all Deaf scientists that follow the official ASL grammar rules.
Three other Deaf people work in my lab. One is a biologist who has worked here for more than 20 years. He’s developed a spreadsheet of scientific words and an explanation of how you sign each one. For example, the sign I use for metastasis starts with both hands facing each other with the fingers bent and moving in a zigzag motion, which indicates disorder, then both hands are extended forward simultaneously, moving apart to represent the cells spreading out.
What’s the sign for ‘centrifuge’? How we added scientific terms to Indian Sign Language
But this is not necessarily the best way to preserve a visual, signed language. Therefore, we are trying to develop a way to film the signs so that interpreters watching the videos can learn them. That would be a much better resource.
All of this has been a lot of work. I would love to have the chance to focus solely on my research, but I’ve been juggling my time between research, creating signs, working with my network of interpreters and everything else. The COVID-19 pandemic added to the problem. Before COVID-19, interpreters worked on site all the time. But now many of them prefer to work remotely. However, interpreting through a video call is not as useful as having an interpreter in the lab. We need them on site for spontaneous conversations when we’re troubleshooting protocols. This has made it even harder to find interpreters who can work at this level of science.
I am feeling burnt out from all this legwork. My energy should be invested in my research and my coursework, not making sure each interpreter understands what’s going on. It’s so much to manage, sometimes I feel like I have earned a PhD in linguistics, too. Continuing research after my PhD is still one of my options, but I’m also looking into project management or consultant jobs that use the knowledge and skills that I have developed.
This interview has been edited for length and clarity.
Bluetooth: v5.2 | ANC: No | Transparency mode: No | Custom EQ: Yes | Charging port: USB-C | Wireless charging: No | Water resistance: IPX2 | Multipoint connectivity: Yes (2 devices) | Wear detection: Yes | Battery life (rated): 5 hrs, 6 hrs w/ wake word off, 20 hrs w/ case | Fast charging: 15 mins = 2 hrs | Codecs: SBC, AAC, aptX | Warranty: 1 year
All of our picks so far are technically earphones, meaning they extend into your ear canal. For some people, that is inherently uncomfortable. Unfortunately, the market for decent yet affordable “earbuds,” which rest on the concha instead of going all the way in your ear, is spotty. If you can’t bring yourself to pay for a pair of AirPods, though, the Amazon Echo Buds are a worthy compromise at $50.
The plastic earpieces here aren’t exactly premium, but they rest lightly in the ear and feel sturdily put together. They let in and leak noise more easily than in-ear headphones, but if you prefer open earbuds, that’s more of a feature than a bug. If the fit doesn’t feel right, you can shed a little bulk by removing the pre-installed silicone covers. (Like most open earbuds, though, comfort here is dependent on your ear shape.) Mic quality is more than adequate, and the circular touch panels give ample room for using the controls, which are customizable and consistently responsive. Battery life sits aroundfive hours, which is middling but not out of character for budget earbuds.The pocket-friendly case adds about three full charges, but it’s worth noting that Amazon doesn’t include a USB-C charging cable. A poor IPX2 water resistance rating means you should avoid the gym with these, too.
While the Echo Buds sound fine out of the box, I’d use the EQ sliders in the Alexa app to bring down the treble a click or two. By default, the highs are a bit too edgy. That said, this emphasis lends a nice crispness to things like vocals, cymbals and strings, and there’s enough separation to keep complex tracks from sounding totally muddled. The profile here isn’t as full-bodied as the latest AirPods, and no open earbuds deliver true sub-bass, but there’s at least some rumble for hip-hop and EDM.
Unlike many cheap earbuds, the Echo Buds support auto-pausing and multi-device pairing. I often had to manually pause playback on one device before I could switch to the other, but having the feature at all at this price is great. Unsurprisingly, they also come with Alexa baked in, which you can access hands-free. You manage the Echo Buds through the Alexa app, which is much more cluttered than a dedicated audio app but includes extras like a lost device tracker and sidetone control for phone calls. And if you want nothing to do with Alexa, it also lets you turn off the mics and wake-word support.
After what feels like a very long wait, all the signs are pointing to an imminent launch for the Sonos headphones – and we just got another big clue that points to them arriving within the next few months.
As per Reddit (via 9to5Mac), the headphones just passed through the approval process at the Federal Communications Commission (FCC) in the US, which means they’ve been given regulatory clearance to go on sale.
There isn’t too much information here – other than they’re headphones, with on-ear cups, and Wi-Fi support – but it usually doesn’t take long for products to go on sale after they’ve been given the go ahead from the FCC.
The latest rumors suggest that June is the month when the Sonos headphones are going to be unveiled, which would fit with them getting FCC clearance in March. There’s also been talk that Sonos could unveil a party speaker at the same time.
What to expect
Patents have revealed what the Sonos headphones might look like (Image credit: Sonos)
While we wait for the Sonos headphones to be made official, we’ve had plenty of leaks about what to expect. Sonos CEO Patrick Spence has gone on the record as saying that a “new product in a multi-billion dollar category” is on the way – hint hint.
Patents already drawn up by Sonos show that these cans are going to come with Wi-Fi connectivity, and it’s clear that you’ll be able to use them with an existing Sonos speaker system pretty seamlessly – switching audio streams between devices as needed.
Other features mentioned in the patents are support for noise cancelling technology, and possibly a digital assistant you can talk to through the headphones. All of this is to be confirmed of course, and plans for products can always change.
As for pricing, the Sonos headphones are apparently going to cost in the region of $449, which works out at about £350 / AU$675. That would undercut what you pay for the AirPods Max, which the Sonos headphones will be challenging.
Four children have remained free of detectable HIV for more than one year after their antiretroviral therapy (ART) was paused to see if they could achieve HIV remission, according to a presentation today at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) in Denver. The children, who acquired HIV before birth, were enrolled in a clinical trial funded by the National Institutes of Health in which an ART regimen was started within 48 hours of birth and then closely monitored for drug safety and HIV viral suppression. The outcomes reported today follow planned ART interruptions once the children met predefined virological and immunological criteria.
“These findings are clear evidence that very early treatment enables unique features of the neonatal immune system to limit HIV reservoir development, which increases the prospect of HIV remission,” said NIAID Director Jeanne Marrazzo, M.D., M.P.H. “The promising signals from this study are a beacon for future HIV remission science and underscore the indispensable roles of the global network of clinicians and study staff who implement pediatric HIV research with the utmost care.”
Advances in ART have significantly reduced perinatal HIV transmission, when a child acquires HIV while in the uterus, during birth, or through consumption of milk from a lactating person. If transmission does occur, children must take lifelong ART to control replication of the virus and protect their immune systems from life-threatening complications. Typically, interruption in treatment will lead to rapid resumption of HIV replication and detectable virus in the blood within weeks. However, in 2013, a case report described an infant born with HIV in Mississippi who initiated treatment at 30 hours of life, was taken off their ART at 18 months of age and remained in remission with no evidence of detectable HIV for 27 months.
Building on the observation that very early ART initiation may limit HIV’s ability to establish reservoirs of dormant virus in infants researchers began an early-stage proof-of-concept study of very early ART in infants conducted in Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the United States, Zambia, and Zimbabwe. Previous publications from the clinical study showed that ART initiated within hours of birth was safe and effective at achieving and maintaining HIV suppression. A small subset of children achieved sustained HIV suppression and met other predefined study criteria for interrupting ART. These criteria include a durable absence of HIV replication from 48 weeks of ART initiation onward, no detectable antibodies near the time of ART interruption, and having a CD4+ T-cell count (the main immune cell target of HIV) similar to those of a child without HIV. Children who met these criteria, were older than 2 years and had stopped consuming human milk were eligible to interrupt ART.
Data presented at CROI summarized the experience of six children, all aged 5 years, who were eligible for ART interruption with close health and safety monitoring. Four of the six children experienced HIV remission, defined as the absence of replicating virus for at least 48 weeks off ART. One of them experienced remission for 80 weeks, but then their HIV rebounded to detectable levels. Three others have been and remain in remission for 48, 52 and 64 weeks, respectively. However, two children did not experience remission, and their HIV became detectable within three and eight weeks after ART interruption, respectively. The two children whose HIV returned at eight and 80 weeks experienced mild acute retroviral syndrome (ARS) with symptoms including headache, fever, rash, swollen lymph nodes, tonsillitis, diarrhea, nausea and vomiting. One child had markedly low white blood cells, which are a type of immune cell. Both the ARS and white blood deficiency resolved either prior to or soon after restarting ART. The three children who experienced viral rebound resumed HIV suppression within six, eight and 20 weeks of restarting ART.
“This is the first study to rigorously replicate and expand upon the outcomes observed in the Mississippi case report,” said lead study virologist Deborah Persaud, M.D., professor of pediatrics at the Johns Hopkins University School of Medicine, and director of the Division of Pediatric Infectious Diseases at Johns Hopkins Children’s Center, Baltimore. “These results are groundbreaking for HIV remission and cure research, and they also point to the necessity of immediate neonatal testing and treatment initiation in health care settings for all infants potentially exposed to HIV in utero.”
The latest findings show that very early ART initiation has varying but favorable outcomes on control of HIV. While ARS was generally mild and resolved in both cases, the authors cautioned that close monitoring for this potential event is needed in ongoing and future HIV remission research involving ART interruption. The children participating in this study took ART regimens with medicines that have been part of standard first-line therapy for decades. Further research is planned or underway to understand how these observations could differ in children receiving newer, more potent generations of antiretroviral drugs, and to identify biomarkers to predict the likelihood of HIV remission or rebound following ART interruption. Additional studies are also needed to understand the mechanisms by which neonatal immunity and very early ART initiation limited the formation of HIV reservoirs and contributed to the remission observed in this study.
“ART shifted the HIV care paradigm, but treatment is a long road, especially for children as lifetime HIV survivors” said Adeodata Kekitiinwa, MBChB, MMed, emeritus clinical associate professor in the Department of Pediatrics at Baylor College of Medicine, study investigator of record and clinical research site leader in Kampala, Uganda. “This trial takes us a step closer to realizing another paradigm shift in which our approach to ART could be so effective that it might be used for a season of life, rather than its entirety.”
This ongoing research is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, which is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH).
The research was led by study co-chairs Ellen Chadwick, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine, and Yvonne Bryson, M.D., professor of pediatrics at the David Geffen School of Medicine and Mattel Children’s Hospital at UCLA, and director of the Los Angeles Brazil AIDS Consortium. Dr. Kekitiinwa, Boniface Njau, M.S., study coordinator at Kilimanjaro Christian Medical Centre in Tanzania and Teacler Nematadzira, MBChB, site investigator at the University of Zimbabwe-University of California San Francisco Collaborative Research Program continue to lead the study teams overseeing care of children who experienced HIV remission. Jennifer Jao, M.D., M.P.H., professor of pediatrics at Northwestern University Feinberg School of Medicine has since assumed a study co-chair role with Dr. Chadwick. The full IMPAACT P1115 study team consists of hundreds of staff across 30 NIAID- and NICHD-supported sites in the 11 study countries.
