Toggle light / dark theme

Atomic switching converts indoles to benzimidazoles in one pot, accelerating drug discovery

Scientists have achieved a new feat in molecular editing by swapping carbon for nitrogen, enabling the direct conversion of indoles into benzimidazoles. This simple switch in a one-pot method offers a hassle-free and effective way of designing medicinally relevant molecules. The work is published in Nature Chemistry.

Single-atom swap reactions require the selective formation and breaking of multiple bonds at the same time, making them quite rare and challenging.

Researchers from ETH Zurich overcame these hurdles by exploiting the electron-rich indole ring’s eagerness to undergo oxidative cleavage via Witkop oxidation. This step can split the electron-rich ring open to form a dicarbonyl intermediate, thereby creating an entry point for subsequent cascade reactions.

Nanoparticles supercharge vinegar’s old-fashioned wound healing power

Wounds that do not heal are often caused by bacterial infections and are particularly dangerous for the elderly and people with diabetes, cancer and other conditions. Acetic acid (more commonly known as vinegar) has been used for centuries as a disinfectant, but it is only effective against a small number of bacteria, and it does not kill the most dangerous types.

New research led by researchers at University of Bergen in Norway, QIMR Berghofer and Flinders University in Australia has resulted in the ability to boost the natural bacterial killing qualities of vinegar by adding antimicrobial nanoparticles made from carbon and cobalt. The findings have been published in the journal ACS Nano.

Molecular biologists Dr. Adam Truskewycz and Professor Nils Halberg found these particles could kill several dangerous bacterial species, and their activity was enhanced when added to a weak vinegar solution.

AI tools fall short in predicting suicide, study finds

The accuracy of machine learning algorithms for predicting suicidal behavior is too low to be useful for screening or for prioritizing high-risk individuals for interventions, according to a new study published September 11 in the open-access journal PLOS Medicine by Matthew Spittal of the University of Melbourne, Australia, and colleagues.

Numerous risk assessment scales have been developed over the past 50 years to identify patients at high risk of suicide or self-harm. In general, these scales have had poor predictive accuracy, but the availability of modern machine learning methods combined with electronic health record data has re-focused attention on developing to predict suicide and self-harm.

In the new study, researchers undertook a systemic review and meta-analysis of 53 previous studies that used machine learning algorithms to predict suicide, self-harm and a combined suicide/self-harm outcome. In all, the studies involved more than 35 million and nearly 250,000 cases of suicide or hospital-treated self-harm.

Karl J. Friston

Professors Karl Friston & Mark Solms, pioneers in the fields of neuroscience, psychology, and theoretical biology, delve into the frontiers of consciousness: “Can We Engineer Artificial Consciousness?”. From mimicry to qualia, this historic conversation tackles whether artificial consciousness is achievable — and how. Essential viewing/listening for anyone interested in the mind, AI ethics, and the future of sentience. Subscribe to the channel for more profound discussions!

Professor Karl Friston is one of the most highly cited living neuroscientists in history. He is Professor of Neuroscience at University College London and holds Honorary Doctorates from the University of Zurich, University of York and Radboud University. He is the world expert on brain imaging, neuroscience, and theoretical neurobiology, and pioneers the Free-Energy Principle for action and perception, with well-over 300,000 citations. Friston was elected a Fellow of the Academy of Medical Sciences (1999). In 2000 he was President of the international Organization of Human Brain Mapping. He was elected a Fellow of the Royal Society in 2006. He became a Fellow of the Royal Society of Biology in 2012 and was elected as a member of EMBO (excellence in the life sciences) in 2014 and the Academia Europaea in (2015).

Professor Mark Solms is director of Neuropsychology in the Neuroscience Institute of the University of Cape Town and Groote Schuur Hospital (Departments of Psychology and Neurology), an Honorary Lecturer in Neurosurgery at the Royal London Hospital School of Medicine, an Honorary Fellow of the American College of Psychiatrists, and the President of the South African Psychoanalytical Association. He is also Research Chair of the International Psychoanalytical Association (since 2013). He founded the International Neuropsychoanalysis Society in 2000 and he was a Founding Editor (with Ed Nersessian) of the journal Neuropsychoanalysis. He is Director of the Arnold Pfeffer Center for Neuropsychoanalysis at the New York Psychoanalytic Institute. He is also Director of the Neuropsychoanalysis Foundation in New York, a Trustee of the Neuropsychoanalysis Fund in London, and Director of the Neuropsychoanalysis Trust in Cape Town.

TIMESTAMPS:
0:00 — Introduction.
0:45 — Defining Consciousness & Intelligence.
8:20 — Minimizing Free Energy + Maximizing Affective States.
9:07 — Knowing if Something is Conscious.
13:40 — Mimicry & Zombies.
17:13 — Homology in Consciousness Inference.
21:27 — Functional Criteria for Consciousness.
25:10 — Structure vs Function Debate.
29:35 — Mortal Computation & Substrate.
35:33 — Biological Naturalism vs Functionalism.
42:42 — Functional Architectures & Independence.
48:34 — Is Artificial Consciousness Possible?
55:12 — Reportability as Empirical Criterion.
57:28 — Feeling as Empirical Consciousness.
59:40 — Mechanistic Basis of Feeling.
1:06:24 — Constraints that Shape Us.
1:12:24 — Actively Building Artificial Consciousness (Mark’s current project)
1:24:51 — Hedonic Place Preference Test & Ethics.
1:30:51 — Conclusion.

EPISODE LINKS:
- Karl’s Round 1: https://youtu.be/Kb5X8xOWgpc.
- Karl’s Round 2: https://youtu.be/mqzyKs2Qvug.
- Karl’s Lecture 1: https://youtu.be/Gp9Sqvx4H7w.
- Karl’s Lecture 2: https://youtu.be/Sfjw41TBnRM
- Karl’s Lecture 3: https://youtu.be/dM3YINvDZsY
- Mark’s Round 1: https://youtu.be/qqM76ZHIR-o.
- Mark’s Round 2: https://youtu.be/rkbeaxjAZm4

CONNECT:

Metal organic frameworks enable a key step toward greener lighting and display technologies

Scientists at Oregon State University have taken a big step toward lighting and display technologies that are more energy efficient and better for the planet. The work centers around crystalline, porous materials known as metal organic frameworks, often abbreviated as MOFs, and points toward next-generation materials that may end reliance on rare earth metals.

The study by Kyriakos Stylianou, associate professor of chemistry in the OSU College of Science, and graduate students Kyle Smith and Ankit Yadav appears in Nature Communications.

The findings are important because displays—ubiquitous in communications, computing, medical monitoring and many other aspects of everyday life—and lighting contribute heavily to global energy consumption and . The that underpin those technologies—europium, terbium, yttrium, cerium, gadolinium and others—are expensive and environmentally hazardous to mine and process.

Scientists map dendritic cell reactions to mRNA vaccines

Belgian scientists have uncovered new details about how the immune system responds to vaccines. Dendritic cells, which are key immune messengers that help kick-start the body’s defenses, show specific responses to lipid nanoparticles. These findings, published in Cell Reports, could lead to safer and more effective vaccines.

Dendritic cells are among the first to detect viruses, bacteria, or other immune challenges. These cells help coordinate the immune system’s response by alerting T cells, the immune system’s soldiers trained to eliminate threats. But dendritic cells don’t always respond in the same way. Some keep the immune system calm and balanced (homeostatic), while others drive a full immune attack (immunogenic).

Until now, little was known about what determines these different responses, especially when dendritic cells encounter vaccines.

Statistical mechanics method helps machines better understand complex systems

A study by University of Hawaiʻi researchers is advancing how we learn the laws that govern complex systems—from predator-prey relationships to traffic patterns in cities to how populations grow and shift—using artificial intelligence (AI) and physics.

The research, published in Physical Review Research, introduces a new method based on to improve the discovery of equations directly from noisy real-world data. Statistical mechanics is a branch of physics that explains how collective behavior emerges from individual particles, such as how the random motion of gas molecules leads to predictable changes in pressure and temperature.

In this new work, statistical mechanics is used to understand how different mathematical models “compete” when trying to explain a system. This matters because many scientific fields rely on understanding how systems change over time, whether tracking disease spread, analyzing or predicting the stock market. But real-world data is often messy, and traditional AI models can be unreliable when the data gets noisy or incomplete.

The Rise of Mechanobiology for Advanced Cell Engineering and Manufacturing

The rise of cell-based therapies, regenerative medicine, and synthetic biology, has created an urgent need for efficient cell engineering, which involves the manipulation of cells for specific purposes. This demand is driven by breakthroughs in cell manufacturing, from fundamental research to clinical therapies. These innovations have come with a deeper understanding of developmental biology, continued optimization of mechanobiological processes and platforms, and the deployment of advanced biotechnological approaches. Induced pluripotent stem cells and immunotherapies like chimeric antigen receptor T cells enable personalized, scalable treatments for regenerative medicine and diseases beyond oncology. But continued development of cell manufacturing and its concomitant clinical advances is hindered by limitations in the production, efficiency, safety, regulation, cost-effectiveness, and scalability of current manufacturing routes. Here, recent developments are examined in cell engineering, with particular emphasis on mechanical aspects, including biomaterial design, the use of mechanical confinement, and the application of micro-and nanotechnologies in the efficient production of enhanced cells. Emerging approaches are described along each of these avenues based on state-of-the-art fundamental mechanobiology. It is called on the field to consider mechanical cues, often overlooked in cell manufacturing, as key tools to augment or, at times, even to replace the use of traditional soluble factors.


Current manufacturing workflows for CAR-based immunotherapies, particularly CAR T, and the emerging CAR NK and CAR macrophage platforms, generally involve four key stages: (i) isolation of primary immune cells or their precursors, (ii) cell activation or differentiation, (iii) genetic modification with CAR constructs, most often via viral vectors or electroporation (EP), and (iv) expansion or preparation for reinfusion. Among these, transfection remains the most critical and technically challenging step, directly influencing the functionality, safety, and scalability of the final product.

In clinical-scale production, EP remains the most widely used non-viral method for gene delivery into immune cells, yet it is increasingly recognized as suboptimal, particularly when delivering large or complex CAR constructs. It suffers from inefficient nuclear delivery, high cell toxicity, and poor functional yields of viable, potent CAR-expressing cells.[ 113 ] These limitations are further exacerbated in more fragile or less permissive cell types, such as NK cells and macrophages, which show lower transfection efficiencies and greater sensitivity to electroporation-induced stress.[ 114 ] Viral vectors, while still dominant in clinical manufacturing, present their own challenges: they are constrained by limited cargo capacity, are costly to produce at scale, and raise regulatory and safety concerns, especially when applied to emerging CAR-NK and CAR macrophage therapies that require flexible, transient, or multiplexed genetic programs.[ 115 ]

In contrast to immune-cell engineering, stem cell-based approaches present a different set of challenges and engineering requirements. While immune cells are genetically modified to enhance cytotoxicity[ 116 ] and specificity or to mitigate excessive T-cell activation,[ 117 ] stem cells must be engineered to control self-renewal, lineage commitment, and functional integration, often requiring precise, non-integrative delivery of genetic or epigenetic modulators (e.g., mRNA, episomal vectors) to maintain cellular identity and safety.[ 118 ] Stem cells hold exceptional therapeutic promise due to their capacity for self-renewal and differentiation into specialized cell types, supporting applications in personalized disease modeling, tissue repair, and organ regeneration.[ 119 ] However, engineering stem cells in a safe, efficient, and clinically relevant manner remains a major challenge. Conventional delivery methods, such as viral vectors and EP, can compromise genomic integrity,[ 120 ] reduce viability,[ 118 ] and induce epigenetic instability,[ 121 ] limiting their translational potential.

New Minimally Invasive Procedure Can Fix Your Heart’s Tricuspid Valve

A Yale interventional cardiologist explains how a new clip can fix a faulty tricuspid valve, relieving symptoms for patients who once had limited options.

There weren’t always good solutions for repairing a faulty tricuspid valve, the valve on the right side of the heart that allows blood to flow from the top chamber to the bottom one. In fact, for many years, a lack of safe and effective treatments contributed to the tricuspid’s nickname: “the forgotten valve.”

For the 1.6 million people in the United States who have tricuspid valve regurgitation, a condition in which a faulty tricuspid valve causes blood to leak backwards (or backflow), medication has difficult side effects, including serious kidney problems. And while open heart surgery can effectively repair the condition, it’s risky for many patients who are older, have tricuspid-related issues such as liver disease, and may have other medical conditions that are more common with age. But without treatment, they experience a poor quality of life, with symptoms such as irregular heart rhythms, fatigue, swelling in the legs, shortness of breath, and, in severe cases, heart failure.

(November 2024)


A Yale Medicine interventional cardiologist discusses a new minimally invasive clip for tricuspid valve regurgitation, a treatment that can help some patients avoid open heart surgery.

Key nervous system components shown to influence gastrointestinal tumor growth

Australian researchers have identified two nervous system components that drive tumor growth in gastrointestinal cancers, creating promising new avenues for treatment with existing approved therapies.

Our gut contains its very own nervous system and is commonly regarded as the second brain. Key players of this system are neuropeptides, the signaling factors that are produced and released by nerves. These factors relay messages throughout our nervous system by connecting to receptors on the outside of cells, influencing a variety of processes.

The team at the Olivia Newton-John Cancer Research Institute (ONJCRI) and La Trobe School of Cancer Medicine discovered that CGRP, a common neuropeptide, and its receptor RAMP1 influence tumor growth in colorectal and stomach cancers.

/* */