Virgin Media is ditching its email services and offering customers a window in which to download their data and move to another email provider. The UK's second-biggest broadband provider is closing its own email service and offering users the option of transferring their addresses and mailboxes to Junara, a service operated by Australian email provider Atmail. Customers who want to retain their Virgin Media email address will be invited to transfer to Junara. The first year will be free for current Virgin Media customers, after which they will have to pay to continue using the service. Virgin Media email users will be contacted directly and given 45 days to sign up with Junara, save their data and move to another provider, or allow their account to close. The change affects all addresses ending in @ntlworld.com, @blueyonder.co.uk, @virgin.net, and @virginmedia.com. Virgin Media stopped issuing new email addresses to broadband customers in 2022, citing the growing popularity of dedicated services such as Gmail and Outlook. A spokesperson for the company told The Register: "As we focus and prioritize our investments and resource on ensuring our customers have the best connectivity experience, we have taken the decision to close the remaining Virgin Media email accounts. We're transferring our email service to Junara, a specialist cloud-based email provider owned by Atmail, giving users a clear route to keep their existing Virgin Media email address if they choose to." "We are writing directly to all impacted customers to clearly explain the changes and will provide a 45-day window to either sign up with Junara, move to an alternative email provider, or close their account. To support users through this transition, all current Virgin Media customers wishing to move to Junara will receive their first year of service free of charge, with additional support available for those who need it." Announcing the change in a blog post, Virgin Media O2 chief operating officer Alan Stott said most people now prefer dedicated email providers to accounts supplied by telecoms operators. "By transferring these email accounts to a specialist provider, we can focus our attention and investment on what we're ultimately here to do – provide fast and reliable broadband, mobile, landline and TV services, and give our customers the best possible experience." Virgin Media has not said how many active email accounts will be affected, but their users will have just 45 days to decide whether keeping their old address is worth signing up for a separate service. ®

A prominent US senator is asking the National Security Agency to provide guidance to the general public on best practices for using virtual private networks to secure their communications from spying by foreign adversaries.

VPNs funnel all of a user’s Internet traffic through an encrypted connection to a remote server. The design provides strong assurances that no one between the user and the server can read the encrypted contents. VPNs also allow users to hide their IP addresses from the destination servers they communicate with. While US agencies have previously recommended use of VPNs, none have given recommendations on which ones provide adequate protection.

It's all in the nuances

There are a host of limitations that can undo many of the protections users may think their VPN provides them. For instance, the encrypted tunnel often terminates once a single server decrypts the traffic and sends it on to its final destination. That means the decrypted traffic or the sending and destination IP addresses may be available for snooping by rogue employees or attackers who hack the server. VPNs also don’t encrypt certain types of metadata, such as time stamps, allowing nation-states to build profiles that can be useful in intelligence gathering.

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As online services get better at blocking malicious traffic, the attackers and scammers behind them have been forced to find new ways to reach their targets. The alternative of choice is now what are known as residential proxy networks. These systems funnel millions of home Internet connections into a unified network, and the proxy operators allow attackers to route their malicious traffic through these connections for a fee. The online services see only IP addresses with good reputations and geolocations that don’t stand out.

More often than not, the home users have no idea that their connections are being used to facilitate crime and occasionally even nation-state attacks. Users who do know often don’t care much. In exchange for leasing out part of their unlimited bandwidth to others, many get free movie and TV show streaming. Several less tech-savvy people I know who own such digital media players have told me, after I explain how the media players piggyback off their connections, that the bonanza of content is worth it. They find the tangible benefits outweigh the abstract harm they pose.

Infecting already compromised devices

Research published Monday brings the threat into much clearer view. Security firm Plume cataloged a vast ecosystem of malware that preys squarely on users of SuperBox, just one of many media players offering pirated content. These malicious apps can be surreptitiously installed by remote attackers even when the devices are positioned behind a router. While Monday’s deep-dive analysis focused exclusively on SuperBox, Plume warned that dozens of similar streaming devices pose precisely the same threat.

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Last month I sat in a networking lab with AWS VP of Global Network Engineering Matt Rehder and cracked a joke about cage nuts cutting your hands to ribbons. I wasn't prepared for the blank stare I got in response, but I really should have been. Mind you, not because the joke wasn't funny (my jokes are hilarious), but rather because the world the joke was referencing no longer exists for them. Racks show up as assembled units, and apparently nobody screws hardware into anything in an AWS datacenter facility these days. It was a peek behind a curtain into a world that powers everything we do in cloud, but that remarkably few of us know exists. My Reg colleague Thomas Claburn toured the lab previously and gave us a deep dive into AWS's paper on this. In summary, "a flat, single-tier network wired in a deliberately near-random pattern leads to a way more resilient network that costs far less to run" and now you're up to speed. The part that I felt didn't get enough attention (and is why I invited myself to tour an AWS facility, much to AWS's surprise) is the economic part and how it impacts AWS customers. In short, their new networking approach can be up to 40 percent more energy efficient, and it's the default for most new datacenter builds (and dear reader, they are building a lot of those these days), and it's been completely invisible both inside and outside of the walls of the world's largest bookstore. The savings and cost efficiencies are real — so where do they go? Cost efficiencies abound Seventeen years ago, Amazon SVP James Hamilton got on stage and pointed out [PDF] that network vendors ran businesses whose margins resembled those of mainframe vendors, who themselves in turn resembled starving pigs at a trough (colorful metaphor mine, but also... not wrong). His big issue with this distilled down to "they're in my way," and he plus his team set out to do something about it. It turns out that "what they did about it" was nothing less than rebuilding the entire networking stack themselves atop commodity hardware. This brings us to a few years ago. Their networking cost efficiencies were already far lower than they would have been running atop traditional networking vendors, and then their Resilient Network Graph shufflebox play took another axe to the cost of networking. So... where have those savings gone over these past few years? I asked point blank whether it was fair to say that they kept the margin improvement rather than passing it back to customers. Their answer was unequivocal: "From a cost perspective? Effectively, yes." AWS cloud economics It's easy to see that answer as damning, but I humbly suggest that if that's your reaction, you haven't been paying attention to broader industry trends these last few years. Unlike its competitors, AWS has not raised prices on existing SKUs. (Yes, the cost of GPU capacity blocks has been raised on a quarterly basis, but that's apparently how those were designed to work, much like a slow version of Spot Instances. And yes, they started charging per public IPv4 address a couple of years ago.) You can go out and spin up the same instance with 64GB of RAM that you could in 2020 and pay the same price today; that's not even increasing a price to keep up with inflation! And while there's a 9 percent increase to go from a Graviton4-based c8g.2xlarge to its equivalent c9g.2xlarge Graviton5 instance, nothing is making you upgrade. Frankly, given the component cost hikes, I'm more than a little astonished that they were able to hold the increase to 9 percent. Further, despite the madness-inducing level of granularity you see in an AWS bill with its millions of SKUs, it's worth noting that each SKU itself obscures dizzying levels of complexity. An EC2 instance charges you per hour (yes, it's metered by the second; do not email me), but that one charge covers the CPU, the RAM, the backplane, the power, the building's physical security, the IAM security bits that keep it from resembling a public computer/something from Microsoft Azure, the employees it takes to build and run these systems, and a stupendous amount of networking magic. A sea change in approach One of those aspects of networking magic is that while it can be usuriously expensive to move traffic between Availability Zones (in major regions each gigabyte has a list price of a penny in and a penny out, so "two cents per gigabyte," which adds up), moving data inside of an AZ remains free. That's impressive when you start to realize how many different datacenter facilities can comprise a single AZ. It's damned impressive when you realize that AZs are expanding, data volumes are increasing, and that expansion comes with costs that thus far AWS has chosen to bear rather than pass on. It's significantly more expensive to move data out of AWS. Their now-defunct Snowball family of devices let you ship data back and forth to AWS. Sending one in cost a set fee, while sending one out cost that fee plus a per-GB charge. Annoying, right? That changed over the last year with the advent of AWS Interconnect - multicloud, which charges you nothing per GB, just an hourly port charge. There's a free tier of one 500 Mbps port per provider, which reduces to zero the AWS-side cost of sending that traffic to GCP, Oracle, and soon Azure. For comparison's sake, it'd be roughly $12,000 to send a month's saturation of that port across the open internet. Stated more plainly, this has never been done before on the AWS side, and it's fascinating. While it's not the primary area of focus for the folks I talked to, I nonetheless asked them about it for an on-the-record answer: "We know customers do not like rate-based network charges because it’s hard to predict their cost, which is why we are moving towards flat-rate pricing for new network products." Well slap me naked and hide my clothes; I'd be less surprised if Matt Garman gave his next re:Invent keynote in iambic pentameter. This bears watching; it's more interesting to me that it comes at a time when prices are rising instead of falling. How hard can it be? Very hard The problem is that a lot of what AWS does is invisible. For example, why am I telling you this instead of AWS? AWS concedes that they're generally bad at telling their own story, but they clearly want to tell it. Historically, they've punted to customers to tell their own stories, on the belief that the benefit will accrue to them. Here's my favorite example: the hard part of a near-random network isn't the cabling so much as the routing. Every protocol you've heard of (BGP, OSPF, a few Cisco-specific protocols that nobody sane uses, etc.) computes shortest paths, and "shortest path" stops meaning much when there are roughly thousands of equivalent routes between any two points. AWS solved that with a protocol called SIDR (Scalable Intent-Driven Routing, pronounced "cider," like the CIDR method for allocating IP addresses because these people are malevolent at naming things) that runs the control plane, while Spraypoint picks up the actual forwarding path. They presented SIDR publicly at re:Invent in 2023, then covered it again at the "Monday Night Live" re:Invent keynote in 2024. Then they published the RNG paper, which doesn't mention SIDR at all. As best I can tell, nobody outside the company has ever connected the protocol to the network it makes possible. I had to ask just in case I was missing something. I'm right. It isn't a secret! They just never got around to mentioning how important it was to making the whole thing go. Unfortunately, their lack of storytelling prowess about these things isn't working for them. The perception runs the other way: the market believes that the neoclouds and the Nvidia reference designs are better. They aren't. You can build a neocloud without knowing much about networking, and some outfits clearly have. A lot of datacenter networks are run by absolute clowns. I know this; I used to be one of said clowns before I got religion / discovered I could pay a cloud provider to make this stuff Matt Rehder's problem. AWS has gotten so good at making network arcana invisible that we don't really stop and think about just how wild it is that you can get damned near full line-rate between any two points in AWS and it just works. In the datacenters you or I build, you get to worry about fun things like "the switch at the top of the rack can only push so much traffic, so not every node can talk at full speed all the time." I have never encountered a real-world scenario of that being a concern in AWS. As a result, when folks set out to build their own datacenters, they don't know what they don't know after a generation of that complexity being hidden away from them, and they approach it with a sense of "how hard could it be?" It is extremely hard, and I have little confidence that the neoclouds spinning up new DC facilities overnight are paying attention to this. I asked Rehder directly whether the "ML datacenter facilities" AWS was launching in places like Mississippi were taking shortcuts since GPU workloads might have different requirements. He looked at me as if I were nuts; every datacenter they build is to the same spec. But customers won't care about that until right after they really should have cared about that; I have faith that a datacenter failure will be sufficiently public, embarrassing, and impactful so as to remind them. The tree of uptime must be periodically refreshed with the blood of massive outages. The humble mumble The folks I spoke to at AWS about this have built something that most of their own customers will never know exists, and they seem generally untroubled by that fact. I found that more admirable than I would have expected to; it's the very definition of thankless work, and AWS shines here. The reason the work is invisible is simply because it succeeds. And they're so humble about it! They politely chuckled at my joke about cage nuts once they got the reference, and I politely chuckled at their joke about how each year's switch is painted the Pantone "Color of the Year," which it turns out was in fact not even slightly a joke. AWS gets a lot wrong. They have ridiculous marketing campaigns, they build five services that do mostly the same thing and then name them like malevolent toddlers, and they've never found a partner they couldn't find a way to compete with. But when it comes to the "chop wood, carry water" type of work that makes the entire cloud possible, the kind that would put most of a keynote audience to sleep, they're the finest in the world. They're just bad at telling the world about it. ®

Police in Mauritius are conducting a criminal investigation into possible forgery related to the annulled June 2025 board election staged by the African Network Information Centre (AFRINIC). AFRINIC is the regional internet registry (RIR) for 54 countries in Africa and the Indian Ocean region. In recent years it has experienced governance and operational problems and been embroiled in a complex set of interlocking legal disputes with one of its members, Cloud Innovation, regarding AFRINIC’s powers to terminate users who do not follow its rules for using IP addresses. The disputes with Cloud Innovation saw AFRINIC unable to convene a board for several years. Courts in Mauritius placed the registry in receivership. The receiver eventually brought the registry into a state that made it possible to stage a board election in June 2025. AFRINIC offered members the chance to vote online, by attending a day of in-person voting in Mauritius, or by appointing a proxy to vote for them at the in-person voting session. During that in-person voting session, the Nomination Committee that oversaw the election became concerned about the voting process and called off the election. AFRINIC’s receiver later annulled the vote, which was re-run under different rules later in the year. AFRINIC has never commented on the reasons for the annulment. The Register sought comment from the four UK-based barristers who comprised the Nomination Committee. None were willing to answer our questions. AFRINIC’s receiver has also not responded to our request for comment. After the annulment, South Africa’s Internet Service Providers' Association (ISPA) made two claims about irregularities at the election: “A duly authorised representative of a resource holder attempting to vote, only to be informed that another person had already submitted a vote on their behalf thanks to a Power of Attorney, which that resource holder had not provided to any third party." "A representative of a resource holder, learning that a Power of Attorney had been submitted on their behalf, only to find that that particular Power of Attorney (the existence of which had already been recorded by AFRINIC staff) had been mysteriously removed from the record by the time a copy was requested.” Mauritius Police this week confirmed to The Register that it is investigating the matter as a possible forgery case. “Two cases related to AFRINIC elections in 2025 are still under investigation at the level of the Central CID of the Mauritius Police Force. Both are alleged Forgery cases,” a spokesperson told The Register. Mauritius Police describes its Central Investigation Division, or Central CID, as “a specialized unit … which deals with sensitive cases and cases involving larger public interest. It deals with all the cases of bribery, fraud and homicides.” And also internet governance election scandals, it seems. AFRINIC revived, revisiting past controversies The court cases that indirectly led to AFRINIC’s annulled election were related to the registry’s powers to terminate users who do not follow its rules. Termination means losing the right to continue using IP addresses allocated by AFRINIC. AFRINIC on Tuesday published an update on the community consultation process it has run to determine members’ interest in, and attitude to, proposed bylaw changes. One proposed change would see AFRINIC add a specific dispute resolution clause to its constitution. Such a clause could perhaps have avoided the lengthy legal battles that the registry continues to fight, but the organization’s Bylaws Review Committee will not recommend adoption of the clause. The Committee also commented on the AFRINIC board’s power to terminate a member, and said it is “considering various options aimed at further strengthening the existing legal safeguards applicable to the exercise of such power.” AFRINIC therefore looks to be trying to strengthen its ability to terminate members, a power that rightly or wrongly has been the source of its many recent travails. The registry also had happier news this week after naming its next CEO: South African lawyer Mike Silber, whose CV includes serving on the board of ICANN and many senior roles at African telcos and tech companies. Silber will take up the position on January 1, 2027, and will clearly have some contentious issues on his desk from day one. ®

ICANN is poring through over 1,600 applications for new global top-level domains (GTLDs) and will reveal which ones it thinks are valid in a few weeks – but hundreds of names applicants hope to secure have already appeared online. GTLDs are the last part of an internet address. The most common and well-known are .com, .net, and .org. In the early 2000s, ICANN allowed a few more GTLDs, and in 2012 ran an open application process that allowed anyone to pay for the privilege of operating their own GTLD. That program saw over 1,900 applications and led to the creation of over 1,200 new GTLDs. Tech companies, including Microsoft, Cisco, and Oracle, scored their own GTLDs. One registry applied for, and won, .sucks – one of many novelty domains that ICANN approved. As The Register reported in May, ICANN this year opened a round of applications for GTLDs and recently announced that it received over 1,600 submissions. The internet governance organization plans a “Reveal Day” in September or October, on which it will publish a list of all applications that have passed administrative checks. Some applicants have jumped the gun and published the list of GTLDs they applied for. The Link Freedom Group has applied for 316 GTLDs, listed here. Among the strings it hopes to turn into GTLDs are .slop, .therapy, and .hype. The outfit also hopes to own .con, .token, and .moon, plus AI-related strings including “agentic” and “AGI”. An unofficial ICANN community Wiki, which The Register understands some applicants have used to share the GTLDs they desire, offers the chance to filter GTLDs in the 2026 application process. It lists the names sought by Link Freedom Group plus hundreds more. Predictably enough, many are strings related to cryptocurrencies, datacenters, AI, or locations in China. ICANN charged an evaluation fee of $227,000 for each submission, and the cost can be higher if a desired string needs extra review due to being considered a highly risky GTLD. It can take months or years for new GTLDs to go live after Reveal Day, because ICANN performs additional reviews and operates a 104-day window in which it considers objections. If you want a domain using any of the GTLDs mentioned above, it’s unlikely registries will be ready to sell you one before late 2027 – and likely rather later than that. ®

Bentham Science Launches Two New Journals to Accelerate Research in Wireless Communications and Engineering

Bentham Science Publishers has announced the launch of two new peer-reviewed journals designed to capture the rapid transformation of modern technology: Wireless and Communication Letters and Current Engineering Letters and Reviews. Both publications are now open for manuscript submissions, offering researchers an international platform to share emerging discoveries in communication systems, engineering technologies, and interdisciplinary innovation. The launches arrive as advances in artificial intelligence, sixth-generation wireless networks, satellite systems, advanced materials, and sustainable engineering continue to reshape scientific research and industrial development.

Wireless and Communication Letters is focused on the technologies that enable today’s increasingly connected world. The journal will publish original letters, full-length research articles, comprehensive reviews, mini-reviews, and guest-edited thematic issues addressing both theoretical developments and practical applications. Its scope covers the complete communication chain, from antennas and radio-frequency hardware to signal processing, network architecture, cybersecurity, and intelligent software. By emphasizing the efficient dissemination of research, the journal aims to provide a rapid channel for findings that could influence the next generation of wireless infrastructure.

The technical challenges addressed by the journal are central to the future of digital connectivity. Fifth-generation networks have already introduced high-speed mobile broadband, ultra-reliable low-latency communication, and massive machine-type connectivity, but researchers are now investigating 6G systems capable of supporting even greater data rates, extremely precise sensing, and seamless integration with artificial intelligence. These systems may combine terahertz frequencies, reconfigurable intelligent surfaces, distributed antennas, edge computing, and advanced machine-learning algorithms. Such technologies require new approaches to spectrum allocation, energy efficiency, network coordination, and data security.

The journal also welcomes research on the Internet of Things and machine-to-machine communication, areas in which billions of sensors and devices are expected to exchange data with minimal human intervention. In these environments, communication protocols must operate reliably despite limited power, unpredictable radio conditions, and enormous numbers of connected nodes. Research into low-power wide-area networks, intelligent scheduling, network virtualization, and secure device authentication could help support applications ranging from industrial automation and smart cities to remote healthcare and environmental monitoring.

A further component of the journal’s scope involves the physical science of communication. Antenna design, electromagnetic propagation, microwave engineering, optical links, and satellite communication determine how information travels through real environments. Engineers must account for obstacles, atmospheric conditions, interference, polarization, bandwidth limitations, and the movement of users or spacecraft. Developments in compact antennas, beamforming, optical wireless communication, and satellite-terrestrial integration could improve connectivity in rural regions, disaster zones, transportation systems, and future space missions.

Wireless and Communication Letters is led by Editor-in-Chief Dr. Nasimuddin of the Antenna and Optical Department at the Institute for Infocomm Research in Singapore. Supported by an international editorial board, the journal states that it will apply a rigorous and objective peer-review process. This is particularly important in a field where theoretical claims must often be tested through simulations, prototypes, channel measurements, or performance comparisons. Research involving modulation, coding, information theory, cognitive radio, software-defined networking, artificial intelligence, privacy, and communication protocols will be considered within the journal’s broad technological remit.

Alongside the communications title, Bentham Science has introduced Current Engineering Letters and Reviews, an interdisciplinary journal intended to connect research across the full spectrum of engineering sciences. Announced on 3 August 2026, the journal will publish research articles, short communications, comprehensive reviews, mini-reviews, and thematic issues. Its mission is to bring together discoveries that are often separated into specialist fields, reflecting the reality that many modern technologies emerge from collaboration among mechanical, electrical, materials, chemical, biomedical, environmental, and computer engineers.

The new engineering journal will cover aerospace, civil, structural, transportation, manufacturing, energy, robotics, automation, nanotechnology, artificial intelligence, and digital engineering. It will also address sustainable engineering, renewable energy systems, smart materials, advanced manufacturing, and biomedical technologies. These subjects are increasingly connected: an electric vehicle, for example, depends simultaneously on materials science, power electronics, software, communications, manufacturing, and transportation engineering. An interdisciplinary publication can provide a forum for examining such systems as integrated technological platforms rather than isolated components.

The scientific importance of this approach is becoming more visible as engineers confront challenges involving climate change, resource efficiency, resilient infrastructure, and automation. Renewable energy systems require improved storage, power conversion, and grid management; smart materials can respond to changes in temperature, pressure, or electromagnetic fields; and artificial intelligence can optimize industrial processes by identifying patterns in large streams of sensor data. At the same time, engineering research must demonstrate reliability, scalability, safety, and economic feasibility if laboratory innovations are to produce measurable benefits in society and industry.

Both journals invite contributions from researchers, engineers, scientists, academics, and industry professionals worldwide. Bentham Science says that information about open-access policies, article processing charges, waiver eligibility, editorial policies, and complaints and appeals procedures is available through the respective journal websites. With their emphasis on rapid communication, technical rigor, and interdisciplinary exchange, the two publications seek to become new hubs for research at the intersection of connectivity, intelligent systems, sustainable technology, and engineering innovation.

Subject of Research: Wireless communications, communication engineering, interdisciplinary engineering research, emerging technologies, artificial intelligence, sustainable engineering, and advanced technological systems.

Article Title: Bentham Science Launches Two New Journals to Accelerate Research in Wireless Communications and Engineering

News Publication Date: 3 August 2026 (for the announcement of Current Engineering Letters and Reviews; no publication date is provided for Wireless and Communication Letters).

Keywords

Wireless communications, 5G, 6G, Internet of Things, satellite communications, antenna design, signal processing, artificial intelligence, engineering research, sustainable engineering, robotics, renewable energy, smart materials, advanced manufacturing.

The federal government is warning users of home and small office routers to secure their devices as Russia state hackers continue to mass-compromise them for use in obscuring nefarious actions against sensitive organizations in the public and private sectors.

Both the Russian and Chinese governments have been compromising routers for years, sometimes in prolonged tugs-of-war to wrest control of devices the other has already commandeered. The US government has occasionally issued covert commands and taken other steps to disinfect routers. Google and other companies have also worked to disrupt the massive botnets that control compromised routers in lockstep. The actions to date are little more than whack-a-mole exercises as the operators simply replace their botnets with new ones.

Proxy networks: The go-to tool

“Russian Federal Security Service (FSB) Center 16 cyber actors continue to exploit poorly configured and vulnerable networking devices worldwide, opportunistically compromising multiple critical infrastructure sector networks,” the Cybersecurity and Infrastructure Security Agency said Monday. The hacking groups are tracked under various names, including Berserk Bear, Energetic Bear, Crouching Yeti, Dragonfly, Ghost Blizzard, and Static Tundra. The advisory was co-issued by governments from around the world, including Australia, Denmark, New Zealand, and the UK.

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In a groundbreaking study poised to reshape our understanding of mitochondrial genetics and neurological disorders, researchers have uncovered profound cortical neuronal disturbances driven by mitochondrial DNA (mtDNA) heteroplasmy in human brain organoids. This revelation centers on the common m.3243A>G mutation, a genetic defect frequently linked to a spectrum of neurodegenerative diseases. The work, published in Nature Communications in 2026 by Hathazi, Lyons, Lagos, and colleagues, offers unprecedented insights into how subtle shifts in mitochondrial DNA populations might disrupt cortical neuron function at a cellular and network level—potentially illuminating new therapeutic avenues for conditions that have long eluded effective treatment.

Mitochondria, often described as the cell’s powerhouses, maintain cellular energy homeostasis by generating adenosine triphosphate (ATP). However, mitochondrial DNA holds a unique genetic code separate from that of the nuclear genome, and it exists in multiple copies within each mitochondrion. Heteroplasmy—an admixture of normal (wild-type) and mutant mtDNA molecules—can fluctuate extensively between cells and tissues. This heterogeneity significantly affects mitochondrial function, but the precise pathological consequences in human neurons have remained elusive. The study by Hathazi and collaborators bridges this gap by meticulously linking mtDNA heteroplasmy directly to measurable disturbances within cortical neurons derived from human organoids.

The researchers employed human pluripotent stem cell-derived cerebral organoids, three-dimensional cellular models that recapitulate many aspects of human cortical development and cellular diversity. By engineering these organoids to harbor varying levels of the m.3243A>G point mutation in the mitochondrial tRNA^Leu(UUR) gene, they generated a physiologically relevant system that models how mtDNA heteroplasmy inherently affects neuronal populations. This mutation impairs mitochondrial protein translation, leading to compromised oxidative phosphorylation—a known driver of metabolic dysfunction in affected cells.

Single-cell analyses revealed marked mitochondrial dysfunction in neurons exhibiting high mutation loads. The mutant mitochondria produced increased reactive oxygen species (ROS), exhibited diminished membrane potential, and showed perturbed calcium handling. These biochemical aberrations culminated in altered electrophysiological properties, including disrupted synaptic transmission and impaired action potential firing patterns. The affected cortical neurons displayed reduced synaptic density and connectivity, phenotypes consistent with impaired network synchronization and cognitive deficits observed in mitochondrial encephalopathies.

Remarkably, the study delineates a threshold effect whereby neuronal function remains relatively preserved below a critical heteroplasmy level but deteriorates precipitously once mutant load surpasses this point. This finding is pivotal in explaining the clinical heterogeneity seen among patients with the m.3243A>G mutation, where symptom severity correlates with mtDNA mutant load. It also underscores the fine balance within mitochondria between normal and mutant genomes that regulates cellular health in the brain.

To establish causality, the investigators utilized gene-editing techniques to reduce the mutant mtDNA proportion within organoids. This intervention partially rescued mitochondrial respiration and restored electrophysiological parameters toward normal, confirming that the mutation-induced mitochondrial defects directly drive neuronal impairment. Pharmacological modulation of mitochondrial stress pathways, such as enhancing mitophagy and antioxidant defenses, further ameliorated neuronal dysfunction, highlighting potential therapeutic strategies.

The implications of these findings extend beyond the m.3243A>G mutation alone. Mitochondrial heteroplasmy is a pervasive phenomenon implicated in aging and numerous neurodegenerative diseases, including Parkinson’s and Alzheimer’s disease. This study suggests that subtle shifts in mitochondrial genetic composition may critically influence disease progression in ways previously unappreciated. Moreover, the use of human cerebral organoids enables modeling of human-specific neuronal vulnerabilities to mitochondrial perturbations, overcoming the limitations inherent in animal models that often lack analogous heteroplasmy dynamics.

The technological advancements leveraged in this research, including high-resolution single-cell mitochondrial assays and precise heteroplasmy editing, represent a tour de force in disease modeling. By recapitulating human cortical development and neuronal network formation in vitro, organoids provide a window into how mitochondrial mutations disrupt developmentally timed neuronal processes leading to widespread cortical dysfunction. These insights could fuel the design of novel mitochondrial-targeted therapies aiming to maintain heteroplasmy below pathological thresholds or to enhance mitochondrial quality control mechanisms.

Furthermore, the findings provoke reconsideration of diagnostic and prognostic approaches in mitochondrial disease. Current clinical assessments largely measure systemic heteroplasmy levels, which may not reflect the mosaicism present within specific brain regions. Non-invasive biomarkers that detect mitochondrial dysfunction in cortical neurons or imaging modalities sensitive to mitochondrial bioenergetics could aid in more accurate disease staging and treatment monitoring.

The study also opens intriguing questions regarding mitochondrial-nuclear genome interactions in the context of heteroplasmy. Given that mitochondrial function is coordinated with nuclear-encoded metabolic pathways, disturbed crosstalk in the presence of mutant mtDNA could exacerbate neuronal pathology. Future research may uncover compensatory nuclear genetic factors that modulate the impact of mtDNA mutations, potentially identifying new therapeutic targets.

In summary, Hathazi and colleagues provide a compelling narrative linking mitochondrial genetic heterogeneity to neuronal network disturbances using a cutting-edge human brain organoid model. This work underscores the critical importance of mtDNA heteroplasmy in shaping neuronal health and disease, particularly within the cerebral cortex, a region central to cognition and behavior. The insights gained promise to accelerate translational efforts aimed at mitigating mitochondrial dysfunction in neurological disorders, paving the way for therapies that restore mitochondrial harmony and preserve brain function.

By marrying sophisticated genetic engineering with organoid technology and comprehensive functional assays, this research sets a new benchmark in mitochondrial neuroscience. The concept that distinct levels of a common mtDNA mutation can finely tune neuronal fate and function introduces a paradigm shift with far-reaching implications. As the field progresses, these findings may herald a future where mitochondrial genomic interventions become integral components of personalized neurotherapeutics, ultimately improving the lives of patients affected by devastating mitochondrial diseases.

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Subject of Research:
Mitochondrial DNA heteroplasmy and its impact on cortical neuronal function in human brain organoids bearing the m.3243A>G mutation.

Article Title:
Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.

Article References:
Hathazi, D., Lyons, C., Lagos, D. et al. Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation. Nat Commun (2026). https://doi.org/10.1038/s41467-026-74103-y

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This is a monumental biological network.

Hidden underground around the world lie 110 quadrillion kilometers of arbuscular mycorrhizal fungal networks—webs of ultra-thin threads that, if connected in a single line, would stretch almost a billion times the distance between the Earth and the sun, according to new research published in Science on Thursday.

These fungal communities form intimate relationships with the roots of plants, which they provide with nutrients like phosphorus and nitrogen in exchange for carbon, 1 billion tons of which the networks sequester underground annually, previous research has found. If the fungal network wasn’t storing it, that carbon would be warming the atmosphere.

But those networks have never been mapped globally until now. The new study led by Society for the Protection of Underground Networks, or SPUN, an organization founded to map mycorrhizal fungi networks, used a combination of literature review, soil samples from around the globe, machine learning and laboratory testing to estimate the distribution and mass of these systems and map where they are densest.

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British small satellite specialist Open Cosmos is seeking more time to deploy its proposed sovereign broadband constellation for Europe after running into launch issues.

The post Open Cosmos seeks deadline extension for broadband constellation appeared first on SpaceNews.

Authorities in the Netherlands said they dismantled a botnet that comprised more than 17 million devices and were managed by 200 servers in a joint operation by the police and the National Cyber Security Center.

The action, announced Thursday, came about after a security researcher reported the sprawling network to authorities. The host infrastructure was located in the Netherlands.

Used for criminal purposes

“The police then seized several botnet servers from a hosting provider for investigation,” the NCSC said. “The botnet was taken offline by the provider because it was used for criminal purposes.”

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© Aurich Lawson / Ars Technica