Lifeboat Foundation

New images from scientists at Cold Spring Harbor Laboratory (CSHL) reveal for the first time the three-dimensional structures of a set of molecules critical for healthy brain function.

The molecules are members of a family of proteins in the brain known as NMDA receptors, which mediate the passage of essential signals between neurons. The detailed pictures generated by the CSHL team will serve as a valuable blueprint for drug developers working on new treatments for schizophrenia, depression, and other neuropsychiatric conditions.

“This NMDA receptor is such an important drug target,” says Tsung-Han Chou, a postdoctoral researcher in CSHL Professor Hiro Furukawa’s lab. That’s because dysfunctional NMDA receptors are thought to contribute to a wide range of conditions, including not just depression and schizophrenia, but also Alzheimer’s disease, stroke, and seizures. “We hope our images, which visualize the receptor for the first time, will facilitate drug development across the field based on our structural information,” Chou says.

It’s important in sports and in interpersonal relationships—perfect timing. But how does our brain learn to estimate when events might occur and react accordingly? Scientists at MPI CBS in Leipzig together with colleagues from the Kavli Institute at the Norwegian University of Science and Technology in Trondheim were able to demonstrate in an MRI study that our brain learns best in connection with constructive feedback.

Imagine playing a game with friends, where they throw you a ball that you must catch. The first couple of throws you might miss the ball, but as you keep trying, you become better at estimating the time it takes to reach you and catch it more easily. How does your brain do this? “Fundamental to this process are your abilities to learn from past experiences and to extract time-related information from the environment,” explains Ignacio Polti, who conducted the study now published in the journal eLife together with Matthias Nau and Christian Doeller.

“Every throw of your friend will be slightly different from the previous one. Some balls arrive earlier, some arrive later. During the game, your brain learns the distribution of arrival times, and it uses this information to form expectations for future throws. By combining such prior knowledge with specific information of our friend’s current throw, we can thus improve the timing of our catch attempts.”

A recent study to be presented at the American Heart Association (AHA) Scientific Sessions 2022 revealed unexpected changes in the electrical conduction system of the first genetically-modified porcine-to-human heart xenotransplant.

Xenotransplantation is the procedure of transplantation/implantation into a human of organs from non-human animal sources. The first pig-to-human heart xenograft was transplanted in January 2022 at the University of Maryland. The recipient survived for 61 days after receiving the xenograft. Research efforts have been underway for this xenotransplantation for over three decades.

Harvesting genetically-modified porcine hearts, the genes of which have been altered for safe transplantation into humans, would become a reality if successful. However, xenotransplantation of organs into a human carries several inherent challenges. With these transplant procedures, there is always the risk of graft rejection, infection, and abnormal heart rhythms.

A team of Canadian researchers from Université de Montréal has designed and validated a new class of drug transporters made of DNA that are 20,000 times smaller than a human hair and that could improve how cancers and other diseases are treated.

Reported in a new study in Nature Communications, these molecular transporters can be chemically programmed to deliver optimal concentration of drugs, making them more efficient than current methods.

Bacterial biofilm formation is a huge problem in industry and medicine. Therefore, the discovery of anti-biofilm agents may hold great promise. Biofilm formation is usually a consequence of bacterial cell–cell communication, a process called quorum sensing (QS). CeO2 nanocrystals (NCs) have been established as haloperoxidase (HPO) mimics and ecologically beneficial biofilm inhibitors. They were suggested to interfere with QS, a mechanism termed quorum quenching (QQ), but their molecular mechanism remained elusive. We show that CeO2 NCs are effective QQ agents, inactivating QS signals by bromination. Catalytic bromination of 3-oxo-C12-AHL a QS signaling compound used by Pseudomonas aeruginosa, was detected in the presence of CeO2 NCs, bromide ions, and hydrogen peroxide. Brominated acyl-homoserine lactones (AHLs) no longer act as QS signals but were not detected in the bacterial cultures.

Measuring the mechanical interplay between cells and their surrounding microenvironment is vital in cell biology and disease diagnosis. Most current methods can only capture the translational motion of fiduciary markers in the deformed matrix, but their rotational motions are normally ignored. Here, by utilizing single nitrogen-vacancy (NV) centers in nanodiamonds (NDs) as fluorescent markers, we propose a linear polarization modulation (LPM) method to monitor in-plane rotational and translational motions of the substrate caused by cell traction forces. Specifically, precise orientation measurement and localization with background suppression were achieved via optical polarization selective excitation of single NV centers with precisions of ∼0.5°/7.5 s and 2 nm/min, respectively.

(https://hannalabweb.weizmann.ac.il/) is a Senior Scientist and Professor in the Department of Molecular Genetics at the Weizmann Institute of Science in Israel, where his lab, and the interdisciplinary group of scientists within it, are focused on understanding the complexity of early embryonic stem cell biology and early developmental dynamics, as well as advancing human disease modeling.

More specifically, Dr. Hanna’s lab investigates the detailed process of cellular reprogramming, in which induced pluripotent stem cells are generated from somatic cells, and they investigate how pluripotency is maintained throughout development in mouse and human. In their studies they employ a diverse arsenal of biological experimentation methods, high throughput screening, advanced microscopy and genomic analyses seeking to combine biological experimentation with computational biology, theory and modeling, to elucidate various biological questions.

Continue reading “Dr. Jacob Hanna, MD, Ph.D. — Synthetic Embryo R&D In Regenerative Medicine & Developmental Biology” »

Mount Sinai researchers have cataloged thousands of sites in the brain where RNA is modified throughout the human lifespan in a process known as adenosine-to-inosine (A-to-I) editing, offering important new avenues for understanding the cellular and molecular mechanisms of brain development and how they factor into both health and disease.

In a study published in Cell Reports, the team described how the rate of RNA editing in the brain increases as individuals age, with implications for dissecting the pathology of altered A-to-I editing across a range of neurodevelopmental and aging disorders.

“Our work provides more nuanced and accurate insights into the contribution of RNA modifications by A-to-I editing during human brain development,” says senior author Michael Breen, Ph.D., Assistant Professor of Psychiatry, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai, and a member of the Seaver Center for Autism Research and Treatment.