Bacterial enzyme research paves the way for acne vaccine

 In a groundbreaking development in the field of anti-acne therapies, a team of researchers at University of California San Diego School of Medicine has created an acne vaccine that successfully reduces inflammation in a mouse acne model. The vaccine neutralizes a specific variant of an enzyme produced by an acne-associated bacteria, while leaving the healthy bacterial enzyme intact.

This work was conducted in collaboration with colleagues at Cedars-Sinai Medical Center and University of California Los Angeles School of Medicine.

Approximately 70 to 80% of individuals develop acne at some point in their lifetime, most often during adolescence, with multiple factors—genetic, environmental and bacterial—to blame.

Through this new work, the scientists are now one step closer to helping drastically reduce the severity of this common condition with a more precise and less disruptive treatment than is presently available.

"We're working to develop a therapy that's much more tailored toward exactly what we know causes acne, rather than just generically blocking inflammation," said George Y. Liu, MD, Ph.D., professor and chief of the Division of Pediatric Infectious Diseases at UC San Diego School of Medicine.

"We hope that by understanding how bacteria induce acne, we can come up with a single or combination vaccine that would take care of acne much more effectively than we can right now."

More than a decade in the making, this research began with an attempt to answer a longstanding question regarding a type of acne-associated bacteria called Cutibacterium acnes (C. acnes), which is plentiful on everyone's skin: If we all have C. acnes on the surface of our skin, then why do only some people develop acne?

In a paper published in Nature Communications, the researchers identified two variants of hyaluronidase, an enzyme produced by C. acnes. One variant, called HylA, is strictly made by C. acnes that are associated with acne. The other variant (HylB) is made by C. acnes associated with healthy skin.

In examining the structural and genetic differences between the two forms of the enzyme, the team found that while HylA worsens acne by causing inflammation, HylB actually appears to reduce inflammation and promote healthy skin. Their work further revealed that HylA and HylB originated from a common ancestor but evolved to have divergent effects.

In particular, the researchers investigated the differences in the way the two variants break down hyaluronic acid in the skin, revealing that HylA produces larger fragments of hyaluronic acid—leading to a more robust inflammatory response—while HylB produces smaller, anti-inflammatory fragments.

When the researchers removed the hyaluronidase genetically from both health- and acne-associated C. acnes, the bacteria became similarly non-inflammatory.

Based on this newfound knowledge, said Liu, who is one of the paper's senior authors, the team then developed therapeutic approaches, including a vaccine and inhibitors, that targeted HylA, the acne-causing variant, and successfully reduced inflammation. The study points to the value of understanding the genetic factors of C. acnes to inform the development of targeted acne treatments.

According to María Lázaro Díez, a former postdoctoral researcher in the George Liu Lab and one of the paper's five lead authors, this novel approach could potentially benefit a large number of acne patients, as there is no specific acne treatment of its type available to date.

"A major strength of this work was the interdisciplinarity and diversity of the team, working together with two common objectives: to expand the knowledge about acne pathogenesis and to use it as an approach for acne therapy," said Lázaro Díez.

The work builds on a 2019 study in which Liu led a team that used a synthetic sebum to develop a new mouse model that closely resembles human acne, allowing them to directly compare "good" and "bad" strains of bacteria.

As the researchers move forward in fine-tuning the use of selective HylA inhibitors and vaccines for acne therapeutics, they are encouraged by this preliminary success and hope to create a product that could be life-changing for many individuals who suffer from acne or are at risk of developing it.

"Our anti-acne directed approach has the potential to revolutionize acne therapies by offering more targeted treatments," said Irshad Hajam, a postdoctoral fellow in the Liu Lab and one of the paper's lead authors.

"What is truly remarkable about this work is we can now have more directed and effective anti-acne therapies while preserving the healthy skin microbiome, and that is a significant advancement in acne therapy."

More information: Irshad A. Hajam et al, Functional divergence of a bacterial enzyme promotes healthy or acneic skin, Nature Communications (2023). DOI: 10.1038/s41467-023-43833-8

https://medicalxpress.com/news/2024-01-bacterial-enzyme-paves-acne-vaccine.html

"Death Toll Of Global War": Weinstein, Carlson Discuss COVID Vax, WHO's Authoritarian Plans For Humanity

 Tucker Carlson sat down with evolutionary biologist Bret Weinstein (brother of Eric Weinstein), where the two dissected the intricate web of narratives surrounding COVID-19, the pharmaceutical industry, and global shifts in governance and public health policy.

According to Weinstein, opposition to the 'official' COVID narratives is like taking on Goliath - with competent and courageous experts in various fields being aggressively censored during the pandemic. This led to the formation of a "Dream Team" of dissenters.

"I call the force that we're up against Goliath. Goliath made a terrible mistake and made it most egregiously during COVID, which is it took all of the competent people, all of the courageous people, and it shoved them out of the institutions where they were hanging on. And it created in so doing, the Dream Team. It created every player you could possibly want on your team to fight some historic battle against a terrible evil," he said, suggesting that the Dream Team is uniquely qualified to fight against those who botched the pandemic response with deadly consequences.

Weinstein also discussed the demonization of alternative treatments such as hydroxychloroquine and ivermectin, and suggested that there have been 17 million deaths from the COVID-19 vaccine.

"So I’m not a math genius, but one in eight hundred shots times billions is a lot of people…..17 million deaths from the COVID vaccine?" asked Tucker. "Just for perspective. I mean, that’s like the death toll of a global war."

To which Weinstein replied: "Yes, absolutely. This is a great tragedy of history. So that proportion. And amazingly there is no way in which it’s over. I mean, we are still apparently recommending these things for healthy children."

Weinstein and Carlson also discussed what they perceive as a global power shift orchestrated through public health policies. They discussed the World Health Organization's (WHO) proposed pandemic preparedness plan, expressing concerns over potential overreach and infringement on national sovereignty. Weinstein warned of a "turnkey totalitarian planet," with the WHO positioned to dictate unprecedented controls over nations and their citizens.

Watch the entire segment on the WHO below...

And subscribers to Tuckercarlson.com can watch the entire one hour interview here.

https://www.zerohedge.com/political/bret-weinstein-and-tucker-discuss-millions-vaccine-deaths-whos-authoritarian-plans

HIV vaccine takes step forward with confirmation of neutralizing antibodies

 The path to a successful HIV vaccine depends on a critical first step—activating specific immune cells that induce broadly neutralizing antibodies.

Reporting Jan. 4 in the journal Cell, a research team led by the Duke Human Vaccine Institute has achieved that requisite initial step in a study using monkeys. The next phase of the work will now move to testing in humans.

"This study confirms that the antibodies are, at the structural and genetic levels, similar to the human antibody that we need as the foundation for a protective HIV vaccine," said first author Kevin O. Saunders, Ph.D., associate director of the Duke Human Vaccine Institute and associate professor in the departments of Surgery, Molecular Genetics and Microbiology, and Integrative Immunobiology.

"We are on the right track," he said. "From here, we just need to begin putting together the additional components of a vaccine."

In earlier work, the research team had isolated naturally occurring broadly neutralizing antibodies from an individual, and then back-tracked through all the changes the antibody and the virus underwent to reach a point of origin for the native antibody and its binding site on the HIV envelope.

With that knowledge, they engineered a molecule that elicits antibodies that mimic the native antibody and its binding site on the HIV envelope.

Four years ago, Saunders and colleagues published a study in Science in which they established that monkeys made neutralizing antibodies when vaccinated with the engineered immunogen, but it was uncertain if those antibodies were like the broadly neutralizing antibody that is needed for a human vaccine.

In the current study, the researchers made a new, more potent formulation of the vaccine and delivered it to monkeys. This time, their goal was to determine whether the neutralizing antibodies generated in the animals were structurally and genetically similar to the antibodies needed in humans. They were.

"We thought we were on the right track in 2019 and we now have atomic-level detail that confirms those findings," Saunders said. "It's an important step forward."

More information: Kevin O. Saunders et al, Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques, Cell (2024). DOI: 10.1016/j.cell.2023.12.002

https://medicalxpress.com/news/2024-01-hiv-vaccine-neutralizing-antibodies.html

How memories are formed in the brain: A new role for the internal compass

 Since their discovery in the 1990s, the head-direction cells in the brain have been referred to as its "internal compass." These cells are activated when the head of an animal or human points in a certain direction, and are thought to be important for spatial orientation and navigation.

Now a team of neuroscientists at the University of Tübingen has discovered that head-direction cells in mice do more than this. They may be involved in relaying sensory and emotional information that is used to form memories of experiences, called "episodic memory."

The research team, led by Professor Andrea Burgalossi from the Institute of Neurobiology and the Werner Reichardt Center for Integrative Neuroscience (CIN), have published their study in the journal Nature Neuroscience.

In the external world of human experience, the senses together contribute to the formation of memories. The visual stimulus of a picturesque landscape, the echo of a laugh, the warmth of a hug—all these sensory impressions are brought together in one region of the brain, the hippocampus. This processing is crucial for transforming fleeting sensory perceptions into lasting memories.

"The hippocampus is a kind of neural curator that integrates the information," says Burgalossi. "During an experience, a memory trace is created in the hippocampus for that episode in our lives."

Previous assumptions called into question

In order to understand more precisely from where sensory information enters the hippocampus, the research team focused on one of its main input structures in the brain, the anterior thalamus.

"We have known for decades that this area is crucial for episodic memory. Patients with damage to this region of the brain suffer from memory loss," says Dr. Patricia Preston-Ferrer, one of the lead authors of the study.

When scientists first recorded the activity of nerve cells in the anterior thalamus of rodents in the 1990s, they discovered the head-direction cells were located there. "Previously, it was assumed that these only encoded the animal's heading direction in its environment," says Preston-Ferrer. "But now our latest experiments show that this idea provides an incomplete picture."

When the Tübingen research team recorded the electrical activity in the mouse brain, they found that the head-direction cells in the thalamus became active when they exposed the mouse to sensory stimuli.

"In the case of a sound being played, as well as in the case of a tactile whisker on the mouse's snout being touched, only the head-direction cells were activated specifically and reliably and with a remarkably short delay," says CIN researcher and co-author of the study Giuseppe Balsamo. "We were surprised, as it had been assumed for decades that these neurons were unresponsive to sensory stimuli."

Possible connection between inner compass and episodic memory

The experiments revealed that in the anterior thalamus, only the head-direction cells responded to sensory stimuli. "This tells us that head-direction cells must have a special function," says CIN researcher and co-author of the study Dr. Eduardo Blanco-Hernandez.

"Their function must go beyond acting as an internal compass." The head-direction cells also responded with increased activity to aroused states including social contacts such as encountering another mouse. "It is known that close attention and emotions have a great influence on the formation of memories and their quality. In such situations, we remember much more vividly than in an uninvolved, passive state," says Blanco-Hernandez.

All in all, the new results indicate that head-direction cells in the thalamus might constitute a key gateway for sensory, attention and arousal information entering the episodic memory system.

"To understand how a memory trace is formed, we need to know the pathways and nerve cells involved that transmit basic information to the hippocampus," says Burgalossi. "Based on our work, we believe the inner compass represents a key node in this process." Whether this node could be influenced, for example for therapeutic purposes, in order to better form and retrieve memories, will require further research.

More information: Eduardo Blanco-Hernández et al, Sensory and behavioral modulation of thalamic head-direction cells, Nature Neuroscience (2024). DOI: 10.1038/s41593-023-01506-1

https://medicalxpress.com/news/2024-01-memories-brain-role-internal-compass.html

Aided by AI, new catheter design helps prevent bacterial infections

 Bacteria are remarkably good swimmers—a trait that can be detrimental to human health. One of the most common bacterial infections in a health care setting comes from bacteria entering the body through catheters, thin tubes inserted in the urinary tract. Though catheters are designed to draw fluids out of a patient, bacteria are able to propel themselves upstream and into the body via catheter tubes using a unique swimming motion, causing $300 million of catheter-associated urinary infections in the U.S. annually.

Now, an interdisciplinary project at Caltech has designed a new type of catheter tube that impedes the upstream mobility of bacteria, without the need for antibiotics or other chemical antimicrobial methods. With the new design, which was optimized by novel artificial intelligence (AI) technology, the number of bacteria that are able to swim upstream in laboratory experiments was reduced 100-fold.

The paper, "AI-aided geometric design of anti-infection catheters," was published in the journal Science Advances on January 3.

In catheter tubes, fluid exhibits a so-called Poiseuille flow, an effect where fluid movement is faster in the center but slow near the wall, similar to the flow in a river's current, where the velocity of the water varies from fast in the center to slow near the banks. Bacteria, as self-propelling organisms, exhibit a unique "two-step forward along the wall, one-step back in the middle" motion that produces their forward progress in tubular structures. Researchers in the Brady lab had previously modeled this phenomenon.

"One day, I shared this intriguing phenomenon with Chiara Daraio, framing it simply as a 'cool thing,' and her response shifted the conversation toward a practical application," says Tingtao Edmond Zhou, postdoctoral scholar in chemical engineering and a co-first author of the study. "Chiara's research often plays with all kinds of interesting geometries, and she suggested tackling this problem with simple geometries."

Following that suggestion, the team designed tubes with triangular protrusions, like shark fins, along the inside of the tube's walls. Simulations yielded promising results: These geometric structures effectively redirected bacterial movement, propelling them toward the center of the tube where the faster flow pushed them back downstream. The triangles' fin-like curvature also generated vortices that further disrupted bacterial progress.

Zhou and his collaborators aimed to verify the design experimentally but needed additional biology expertise. For that, Zhou reached out to Olivia Xuan Wan, a postdoctoral scholar in the Sternberg laboratory.

"I study nematode navigation, and this project resonated deeply with my specialized interest in motion trajectories," says Wan, who is also a co-first author on the new paper. For years, the Sternberg laboratory has conducted research into the navigation mechanisms of the nematode Caenorhabditis elegans, a rice grain–sized soil organism commonly studied in research labs and thus had many of the tools to observe and analyze the movements of microscopic organisms.

The team quickly transitioned from theoretical modeling to practical experimentation, using 3D printed catheter tubes and high-speed cameras to monitor bacterial progress. The tubes with triangular inclusions resulted in a reduction of upstream bacterial movement by two orders of magnitude (a 100-fold decrease).

The team then continued simulations to determine the most effective triangular obstacle shape to impede bacteria's upstream swimming. They then fabricated microfluidic channels analogous to common catheter tubes with the optimized triangular designs to observe the movement of E. coli bacteria under various flow conditions. The observed trajectories of the E. coli within these microfluidic environments aligned almost perfectly with the simulated predictions.

The collaboration grew as the researchers aimed to continue improving the geometric tube design. Artificial intelligence experts in the Anandkumar laboratory provided the project with cutting-edge AI methods called neural operators.

This technology was able to accelerate the catheter design optimization computations so they required not days but minutes. The resulting model proposed tweaks to the geometric design, further optimizing the triangle shapes to prevent even more bacteria from swimming upstream. The final design enhanced the efficacy of the initial triangular shapes by an additional 5% in simulations.

"Our journey from theory to simulation, experiment, and, finally, to real-time monitoring within these microfluidic landscapes is a compelling demonstration of how theoretical concepts can be brought to life, offering tangible solutions to real-world challenges," says Zhou.

More information: Tingtao Zhou et al, AI-aided geometric design of anti-infection catheters, Science Advances (2024). DOI: 10.1126/sciadv.adj1741

https://medicalxpress.com/news/2024-01-aided-ai-catheter-bacterial-infections.html

The one item nurses say every parent should have if their child is in need of first aid

 Baby first aid course CPR Kids has revealed a useful tip about how to help children with a fear of blood.

In their most popular reel of 2023, the group of nurses showed the benefits of a red towel around the house, which blends the color of blood into the fabric and makes it more difficult to detect.

“They can help with the fear and anxiety some little (and big) ones get from seeing blood,” they wrote on Instagram.

They said this helps to make dealing with nose bleeds or cuts easier.

“If you or your little one don’t like the sight of blood or if your little one completely freaks out at even a drop, these are a necessity.”

One user found this useful, due to their son having chronic immune thrombocytopenic purpura (ITP).

“We get regular nose bleeds and I had never thought of this!” she said.

CPR Kids was created by pediatric nurse Sarah Hunstead as a means of teaching parents how to treat their kids in the crucial minutes before an ambulance arrives in an emergency.

Her team regularly posts about various topics that affect parents and their young, with an active Instagram account and regular blog posts.

Their most popular post online last year was about the dangers of swinging your kids by their arms, and how it can result in ‘pulled elbow.’

Pulled elbow is when a kid’s lower arm can be pulled out of its elbow joint, which needs to be put back into place by a medical professional.

“We don’t want to be the fun police with this one – we promise!” they wrote. “You don’t have to stop the fun, just lift them by their armpits instead!”

Their most popular blog post discussed the cause of red or brown strings in a baby’s poo, which is very commonly just banana.

Hunstead mentioned getting this question many times during her period as a nurse, and the same question is asked often in her classes.

Other recent blog posts include topics such as skincare products, cold sores, car seat safety and the myths behind baby walkers.

“Not only are baby walkers dangerous from an injury risk perspective,” wrote Casey De Farria on the site’s blog, “but using a walker can delay independent walking.”

https://nypost.com/2024/01/06/lifestyle/the-one-item-nurses-say-every-parent-should-have-if-their-child-is-in-need-of-first-aid/

'White House scrambles as Navajo Nation protests transport of remains to sacred moon'

 The Navajo Nation is trying to ground the first commercial burials in space, insisting that the plan to memorialize humans on the moon will turn a place sacred to native religions into a “waste site.”

The Biden administration stepped in Friday to defuse the brewing star war, CNN reported, calling a hasty White House meeting ahead of the scheduled Monday launch of a rocket set to send the remains of George Washington, John F. Kennedy, and a constellation of “Star Trek” idols into space.

“The moon holds a sacred place in Navajo cosmology,” said Navajo president Buu Nygren.

“The suggestion of transforming it into a resting place for human remains is deeply disturbing and unacceptable to our people.”

“We’re turning the moon into a graveyard and we’re turning it into a waste site,” said Justin Ahasteen of the Navajos’ Washington office.

The two-stage Vulcan Centaur rocket has been packed with the remains of 333 people, including the late “Star Trek” creator Gene Roddenberry, his wife, recurring cast member Majel Barrett-Roddenberry, several fellow USS Enterprise actors, and others whose families paid for the privilege.

3

A political Death Star could keep the remains of George Washington, John F. Kennedy, and a constellation of “Star Trek” idols earthbound as Native Americans claim the moon as their own sacred site.

3

The Biden administration scrambled to soothe angry members of the Navajo Nation with a hastily called White House meeting Friday, CNN reported.Astrobotic Technology

Hair samples from three US presidents — Washington, JFK, and Dwight D. Eisenhower — are also aboard, courtesy of Celestis, a privately owned space burial company.

“We reject the assertion that our memorial spaceflight mission desecrates the moon,” said Celestis CEO Charles Chafer.

“Our memorial on the moon is handled with care and reverence … No one, and no religion, owns the moon.”

3

“The moon holds a sacred place in Navajo cosmology,” said Navajo president Buu Nygren.The Navajo Nation Office of the President

A 6-foot-tall, 8-foot-wide Peregrine Lunar Lander will drop 62 sets of human remains, packed separately in titanium capsules, on the moon’s surface.

The rest will continue into deep space to orbit around the sun.

But the native objections could short-circuit the mission, which has already been beset by delays.

https://nypost.com/2024/01/06/news/white-house-scrambles-as-navajo-nation-protests-transport-of-george-washington-jfk-and-other-remains-to-sacred-moon/