Delivering macromolecules across biological barriers such as the blood–brain barrier limits their application in vivo. Previous work has demonstrated that Toxoplasma gondii, a parasite that naturally travels from the human gut to the central nervous system (CNS), can deliver proteins to host cells. Here we engineered T. gondii’s endogenous secretion systems, the rhoptries and dense granules, to deliver multiple large (>100 kDa) therapeutic proteins into neurons via translational fusions to toxofilin and GRA16. We demonstrate delivery in cultured cells, brain organoids and in vivo, and probe protein activity using imaging, pull-down assays, scRNA-seq and fluorescent reporters. We demonstrate robust delivery after intraperitoneal administration in mice and characterize 3D distribution throughout the brain. As proof of concept, we demonstrate GRA16-mediated brain delivery of the MeCP2 protein, a putative therapeutic target for Rett syndrome. By characterizing the potential and current limitations of the system, we aim to guide future improvements that will be required for broader application.
Tag: science
‘Digital Twin’ Of Earth Being Created To Predict The Future, Micro-Manage Everything
How do you know when a small-scale farmer in Africa, Latin America or Asia has sufficiently adapted to longer droughts or shifts in traditional monsoon seasons?
The complexity of this question means it is often left unanswered, with funding for such adaptation in developing countries dropping to around just a quarter of total climate finance provided by developed countries.
Delegates gathering at the Bonn Climate Change Conference to prepare for this year’s UN climate talks will be anticipating such questions, with COP29 already dubbed the “finance COP”.
In Baku, Azerbaijan, later this year, countries are expected to discuss a new climate finance deal after reaching the target of $100 billion (€93.2bn) a year in finance for developing countries two years later than agreed.
Historically low-emitting countries across much of the Global South desperately need more financial support to improve their climate defences across key sectors such as agriculture.
Less than 1% of international climate finance was spent helping smallholder farmers adapt to climate change in 2021, with many forced to spend up to 40% of their own incomes to cope with floods, droughts and crop pests.
However, in addition to more finance, countries across Africa, Asia, and Latin America also need ways of measuring adaptation to direct investments more effectively.
Study Confirms — Trans Fats Policy Killed Millions
For the past six decades, saturated fats and cholesterol have been wrongly vilified as the central culprit of heart disease, stroke and peripheral vascular disease. However, research has demonstrated that it’s actually trans fats and processed vegetable oils found in many processed foods that are the real enemy.
In the decades saturated fats were demonized, the food industry responded by replacing saturated fats with more shelf-stable trans fats and a new market of low-fat (high-sugar) foods was born.
Americans’ health has plummeted ever since, and millions have been prematurely killed by this mistake. Making matters worse, genetically engineered soy oil, which is a major source of trans fat, can oxidize inside your body, thereby causing damage to both your heart and your brain.
One of the first articles published exonerating saturated fats was in 1957 by the late Dr. Fred Kummerow,1 who spent eight decades absorbed in the science of lipids and heart disease. In 2013, Kummerow sued the U.S. Food and Drug Administration (FDA) for not withdrawing trans fats from the market.2 It was Kummerow’s lifetime work that revealed the dangers of trans fat and oxidized cholesterol and the relationship to heart disease.
Not surprisingly, trans fat is also linked to dementia as the arterial changes that occur in the heart muscle also occur in the brain, triggering neurological damage. Research has demonstrated the dangers to health and a great financial burden that eating a diet with trans fat has placed on the American public.
Government Conducts Brutal Dog Experiments, Congress Writes Strongly Worded Letter
Nothing exceeds like excess, the U.S. government being the largest flusher of taxpayer cash — confiscated at gunpoint, by the way — down the toilet in world history.
But it’s not just wasted money — it’s wasted money used to torture innocent animals with no discernible public benefit, all in the name of The Science™, In Which We Trust.
Related: Washington Post Admits It Lied About Fauci’s Beagle Torture Regime — For Years
Via White Coat Waste Project (emphasis added):
“Since the 1980s, DOD policy has banned the use of dogs (and cats and primates) in trauma training and weapons experiments, but we’ve exposed a loophole that’s allowed the agency to continue torturing dogs in other testing.
Now, we’re setting our sights on the DOD’s dog abuse and have exposed how it’s wasting $1 million to butcher beagles in completely unnecessary and cruel drug tests.
According to federal spending databases, the U.S. Army has recently commissioned a $949,108 experiment on beagles in which the animals will be forced to ingest massive doses of an experimental drug for the alleged purpose of winning FDA approval. These tests typically abuse dozens of puppies and they’re killed and dissected at the end…
However, the FDA has stated clearly that it, ‘does not mandate that human drugs be studied in dogs’ And the DOD even admits, ‘animal models have limited relevance to humans and poorly predict effects in humans.’”
The letter penned by 25 Congressional members reads as follow (emphasis added):
“We are writing to obtain additional information regarding the Department of Defense’s (DoD) funding of seemingly unnecessary and inhumane experiments on dogs.
An investigation by the watchdog group White Coat Waste Project reported in May 2024 that the DoD recently spent approximately $949,000 to commission a three-month-long drug toxicity study using beagle dogs. This kind of drug toxicity testing typically involves forcing puppies to ingest large doses of experimental compounds daily for 13 weeks, after which they are killed. With the contract beginning on August 1, 2023, and scheduled to end on July 31, 2024.
Pyramid Power: Technology Resembling World’s Most Famous Ancient Structure Leads to Game Changer in Optical Communication
A potentially revolutionary new technology that could greatly advance optical communications, surveillance, and photonic device isolation has something in common with the most captivating construction design of the ancient world: the pyramid.
Researchers at UCLA have produced a revolutionary new design for diffractive deep neural networks, or D2NNs, that they say significantly enhances unidirectional image magnification and demagnification. Dubbed Pyramid D2NNs, the new design architecture lives up to its name by introducing a pyramid-structured network that offers high-fidelity image formation while reducing refractive features, all by aligning its layers in the same direction of image magnification and demagnification.
What Are Diffractive Deep Neural Networks?
D2NNs are constructed from individual transmissive layers that are optimized through deep learning, allowing them to perform computation almost entirely through the use of optics.
In their recent research, the UCLA team, led by Professor Aydogan Ozcan, worked with a pyramid-shaped diffractive optical network, a design that allowed the team to achieve unidirectional imaging with fewer diffractive degrees of freedom.
The result is a design that helps to ensure high-fidelity image formation, but only in one direction. By contrast, significant image inhibition occurs in the opposite direction, conditions that are key for use with applications where imaging in one direction (i.e., unidirectional imaging) is required. Such fields include defense and security technologies, telecommunications applications, and systems used for privacy protection.
US, UK accelerate quantum computing programs after China breakthrough
Scientists and lawmakers in the United States, United Kingdom and European Union are ramping up efforts to advance quantum computing in the West after scientists in China observed what appears to be the world’s first room-temperature time crystals.
A team of physicists hailing primarily from Tsinghua University in China, with contributions from scientists in Denmark and Austria, published peer-reviewed research on July 2 detailing the creation and observation of room-temperature time crystals.
In the month since the paper was published, quantum research labs in the West have announced numerous initiatives to extend existing efforts in the field of quantum computing and to create new research partnerships.
Room-temperature time crystals
Time crystals are a unique state of matter originally proposed by physicist Frank Wilczek in 2012. They work similarly to other crystals, such as snowflakes or diamonds, which are created when specific molecules form lattice-like bonds that repeat through space.
In time crystals, however, the molecules bond in time. Instead of locking into a crystalline structure that repeats, a time crystal’s molecules flicker back and forth between different configurations like a GIF on a loop.
Back in 2021, an international team of scientists working with Google’s quantum computing lab simulated time crystals using a quantum computer. This breakthrough demonstrated the potential for quantum computers to explore exotic states of matter and set the stage for the convergence of quantum tech and time crystals.
Now, in July 2024, the Tsinghua team appears to have created time crystals at room temperature. This, theoretically, allows time crystal technology to be employed in non-laboratory equipment and could serve as a massive accelerator for the development of useful quantum computers.
Former NASA Scientist Doing Experiment to Prove We Live in a Simulation
Could we be trapped inside a simulated reality, rather than the physical universe we usually assume?
It’s a tantalizing theory, long theorized by philosophers and popularized by the 1999 blockbuster “The Matrix.” What if there was a way to find out once and for all if we’re living inside a computer?
A former NASA physicist named Thomas Campbell has taken it upon himself to do just that. He devised several experiments, as detailed in a 2017 paper published in the journal The International Journal of Quantum Foundations, designed to detect if something is rendering the world around us like a video game.
Now, scientists at the California State Polytechnic University (CalPoly) have gotten started on the first experiment, putting Campbell’s far-fetched hypothesis to the test.
And Campbell has set up an entire non-profit called Center for the Unification of Science and Consciousness (CUSAC) to fund these endeavors. The experiments are “expected to provide strong scientific evidence that we live in a computer-simulated virtual reality,” according to a press release by the group.
Needless to say, it’s an eyebrow-raising project. As always, extraordinary claims will require extraordinary evidence — but regardless, it’s a fun idea.
Lesser-Known Cannabis Component CBG Linked To Improved Memory And Reduced Anxiety, First-Ever Human Trial Finds
A lesser-known cannabinoid known as CBG has surprised scientists after a first-ever human clinical trial found that it appears to improve memory, while also “significantly” reducing anxiety and stress.
The non-intoxicating cannabinoid might not be as well-known as THC and CBD, for example, but as it’s grown in popularity, researchers at Washington State University (WSU) and the University of California at Los Angeles (UCLA) set out to investigate its therapeutic potential amid anecdotal, survey-based reports about its therapeutic potential.
The study, published in the journal Scientific Reports this month, found that cannabigerol, or CBG, caused a “significant overall reductions in anxiety as well as reductions in stress” among study participants compared to the placebo. “CBG also enhanced verbal memory relative to placebo,” with “no evidence of subjective drug effects or impairment.”
That finding about CBG’s effects on memory took the research team by surprise. Lead author and WSU associate professor of psychology Carrie Cuttler said in a press release that they “triple-checked to ensure accuracy, and the enhancement was statistically significant.”
Complex Life on Earth May Be 1.5 Billion Years Older Than We Thought
There’s still some scientific debate over when exactly complex life forms appeared on Earth, and the latest research suggests previous estimates need to be revised – by about 1.5 billion years, in fact.
That’s based on a new analysis of marine sedimentary rocks in the Franceville Basin off the west coast of Africa that were deposited some 2.1 billion years ago.
The general consensus is that animals first showed up around 635 million years ago. Now, an international team of researchers has discovered that the rock samples indicate increased phosphorus and oxygen in the seawater, which has previously been linked to accelerations in evolution.
“We already know that increases in marine phosphorus and seawater oxygen concentrations are linked to an episode of biological evolution around 635 million years ago,” says Earth scientist Ernest Chi Fru from Cardiff University in the UK.
“Our study adds another, much earlier episode into the record, 2.1 billion years ago.”
An unusually substantial number of fossils large enough to be seen without a microscope have been discovered in the Franceville Basin, and it’s not clear what we’re to make of them. Earlier studies have also suggested these macrofossils point to the first complex life on the planet.
Here, the researchers link the nutrient enrichment of the water to the collision of two ancient continents, which then created a shallow inland sea and the conditions for cyanobacterial photosynthesis, a chemical process that would’ve led to an underwater environment more conducive to biological complexity.
This would have created a natural laboratory for organism diversity and evolutionary leaps in size and structure, the researchers contend. However, because the body of water was isolated, these more sophisticated forms of life wouldn’t have spread elsewhere or survived to the next jump forward.
Life on Venus? New Discovery Deepens Controversy Over Possible Signs of Life in Planet’s Atmosphere
Recent observations of Venus have yielded new evidence of a compound in its atmosphere that could indicate the presence of life, according to findings that potentially lend weight to controversial past discoveries.
Phosphine, a toxic gas that astrobiologists have proposed could be associated with the presence of life on rocky planets, was initially detected in Venus’s atmosphere in a surprise discovery four years ago. Now, new observations potentially strengthen those past findings, hinting at the presence of biosignatures that, if confirmed, could mean life forms are able to thrive in the planet’s harsh environment.
A Controversial Discovery on Venus
The initial detection of phosphine in Venus’s oxidized atmosphere was reported in September 2020, when a team of scientists led by Jane Greaves of Cardiff University said they had found evidence of the toxic molecule. The discovery initially led to debate over the possibility that life could exist on Venus, since phosphine is normally associated with organisms that thrive in low-oxygen environments.
The team’s announcement received considerable media attention, and also led to controversy that culminated in rebukes from some in the scientific community. Arguably, the sharpest criticism was leveled by the organizing committee of the International Astronomical Union (IAU) Commission F3 on Astrobiology, who even questioned the ethics of Greaves and her team over the manner in which the discovery was revealed.
“It is an ethical duty for any scientist to communicate with the media and the public with great scientific rigour and to be careful not to overstate any interpretation which will be irretrievably picked up by the press,” the commission wrote in an official statement released at the time.
The commission added it “would like to remind the relevant researchers that we need to understand how the press and the media behave before communicating with them.”
Initial follow-up attempts to detect the compound again were unsuccessful. However, last year, Greaves and her team succeeded in detecting phosphine in deeper portions of the planet’s atmosphere during observations made with the James Clark Maxwell Telescope (JCMT) at Mauna Kea Observatory, Hawaii. Additional detections with NASA’s Stratospheric Observatory for Infrared Astronomy (SOFIA) also suggested the presence of phosphine, which may originate either within or from below the clouds on Venus.
Hellbound and Down 
You must be logged in to post a comment.