Lifeboat Foundation

ICYMI: In a groundbreaking achievement, researchers have successfully created a chimeric monkey with two different sets of DNA through the injection of stem cells from one monkey embryo into another of the same species.

[Source]

Scientists based in China have successfully created a chimeric monkey.

Continue reading “China creates world’s first chimeric monkey with fluorescent eyes, fingertips” »

For many people struggling with obesity, the drug is a potential lifesaver. Excess weight is associated with higher incidences of stroke, heart and liver disease, sleep apnea, joint problems, and some cancers. A major clinical trial this year in tens of thousands of overweight people without diabetes found the main ingredient in Ozempic, semaglutide, reduced the risk of stroke and heart attack, while lowering the chances of death due to cardiovascular problems.

Perhaps even more importantly, the drug is gradually changing societal views on obesity—it’s not due to lack of will power, but a chronic medical condition that can be treated.

But Ozempic and similar drugs—like Wegovy, another semaglutide-based medication that has been FDA-approved for weight loss—are already set for the next chapter: tackling a wide range of brain disorders, including Alzheimer’s and Parkinson’s. Clinical trials are underway for addiction, and the drugs are showing early promise battling bipolar disorder and depression.

Occam’s razor—the principle that when faced with competing explanations, we should choose the simplest that fits the facts—is not just a tool of science. Occam’s razor is science, insists a renowned molecular geneticist from the University of Surrey.

In a paper published in the Annals of the New York Academy of Sciences, Professor Johnjoe McFadden argues Occam’s razor—attributed to the Surrey-born Franciscan friar William of Occam (1285–1347)—is the only feature that differentiates science from superstition, pseudoscience or fake news.

Professor McFadden said, “What is science? The rise of issues such as vaccine hesitancy, climate skepticism, alternative medicine, and mysticism reveals significant levels of distrust or misunderstanding of science among the general public. The ongoing COVID inquiry also highlights how scientific ignorance extends into the heart of government. Part of the problem is that most people, even most scientists, have no clear idea of what science is actually about.”

A microbial sensor that helps identify and fight bacterial infections also plays a key role in the development of blood stem cells, providing a valuable new insight in the effort to create patient-derived blood stem cells that could eliminate the need for bone marrow transplants.

The discovery by a research team led by Raquel Espin Palazon, an assistant professor of genetics, development and cell biology at Iowa State University, is published in Nature Communications. It builds on prior work by Espin Palazon showing that the inflammatory signals that prompt a body’s immune response have an entirely different role in the earliest stages of life, as vascular systems and blood are forming in embryos.

Espin Palazon said knowing that embryos activate the microbial sensor, a protein known as Nod1, to force vascular endothelial cells to become blood stem cells could help develop a method to make blood stem cells in a lab from a patient’s own blood.

Targeted protein degradation (TPD) is an emerging therapeutic modality and has attracted great attention from academia and industry^1,2. The prototypical TPD agents, molecular glues (MGs) and proteolysis targeting chimeras (PROTACs), can lead to temporal proteasomal degradation of the protein-of-interest (POI). PROTACs are small heterobifunctional molecules integrating an E3-ligase binder and a POI binding moiety through a synthetic linker construct. The PROTACs technology has been applied to degrade numerous pathological proteins and a rich pipeline is currently progressing into preclinical and early clinical trials^3,4,5. However, overcoming PK/PD issues towards clinical compounds is demanding due to the intrinsically high molecular weight and related physicochemical properties⁶. On the other hand, MGs are small molecules with beneficial ‘drug-like’ physicochemical properties binding to an E3 ligase, and, similarly to PROTACs, leading to neosubstrate proteasomal degradation. Their mechanism of action is however less predictable; their often hydrophobic surface-exposed portions of the MGs seem to change the hydrophobic surface area of the E3 ligase and thereby leading to neosubstrate ubiquitination and degradation^7,8. MGs have already proven their validity as marketed drugs, as there are several approved drugs or clinical compounds working by an MG mechanism (Fig. 1A), for example, the IKZF1/3 degrader thalidomide and its analogs pomalidomide and lenalidomide⁸, and the RBM39 degrader indisulam⁹. Thalidomide analogs induce selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase¹⁰. Additionally, CSNK1A1 (CK1α) was recently discovered as a lenalidomide-specific neo-substrate¹¹. Interestingly, modification of pomalidomide or lenalidomide can have a profound impact on the degradation potency and degradation profiles. For example, CC-220 (Fig. 1A) showed 10-fold more potency in the cells than lenalidomide, and CC-885 (Fig. 1A) was found to induce degradation of the substrate GSPT1^12,13. Both MGs and PROTACs are emerging drug modalities providing interesting features over classical pharmacology-driven drugs by their ability to drive the destruction of proteins that have multiple functions, thereby potentially overcoming resistance mechanisms and providing new pharmacology. While PROTACs can be developed highly rationally, MGs are discovered rather serendipitously requiring synthesis and testing of large series of compounds^14,15. Additionally, the discovery of MGs and PROTACs is done in a sequential, often mmol scale synthesis which is time-consuming and expensive.

In this work, to address current shortcomings in MGs discovery, we use the direct-to-biology (D2B) approach and combined the automated, high throughput miniaturized synthesis with cell-based phenotypic screening (Fig. 1B). The I.DOT (Immediate Drop on Demand Technology, a pressure-based nano dispensing technology) is employed to accelerate the synthesis of diverse MGs libraries on nano scale^{16,17,18,19,20,21}. In a subsequent cell-based phenotypic screening cascade, the compounds are tested in the thalidomide and analog sensitive MM.1S multiple myeloma cell line which reportedly is used for MGs screening²². In this D2B screening platform, the crude compounds are directly screened on cells without further chromatographic purification or clean up. Then, the 19 best compounds are selected for re-synthesis on mmol scale followed by purification and fully characterized.

A biohybrid, leaf-spring design of DNA origami functions as a pulsating nanoengine that exploits the DNA-templated RNA transcription mechanism while consuming nucleoside triphosphates as fuel. The nanoengine also drives a nanomechanical follower structure.

Scientists may have found a more efficient water to desalinate water using solar power, according to new research, offering a solution for global water scarcity through the use of renewable energy.

Researchers at Nankai University in Tianjin, China, developed the concept of a solar-powered desalination system that produces fresh water by using smart DNA hydrogels that does not consume additional energy, compared to conventional desalination strategies currently in use, such as reverse osmosis, which use copious amounts of energy, according to a paper published in the journal Science Advances on Thursday.

The same process can be used simultaneously to extract uranium from seawater or treat uranyl containing nuclear wastewater, the researchers said.

When it comes to delivering drugs to the body, a major challenge is ensuring that they remain in the area they’re treating and continuing to deliver their payload accurately. While major strides have been made in delivering drugs, monitoring them is a challenge that often requires invasive procedures like biopsies.

Researchers at NYU Tandon led by Jin Kim Montclare, Professor of Chemical and Biomolecular Engineering, have developed proteins that can assemble themselves into fibers to be used as therapeutic agents for the potential treatments of multiple diseases.

These biomaterials can encapsulate and deliver therapeutics for a host of diseases. But while Montclare’s lab has long worked on producing these materials, there was once a challenge that was hard to overcome—how to make sure that these proteins continued to deliver their therapeutics at the correct location in the body for the necessary amount of time.

The delivery of drugs to specific target tissues and cells in the brain poses a significant challenge in brain therapeutics, primarily due to limited understanding of how nanoparticle (NP) properties influence drug biodistribution and off-target organ accumulation. This study addresses the limitations of previous research by using various predictive models based on collection of large data sets of 403 data points incorporating both numerical and categorical features. Machine learning techniques and comprehensive literature data analysis were used to develop models for predicting NP delivery to the brain. Furthermore, the physicochemical properties of loaded drugs and NPs were analyzed through a systematic analysis of pharmacodynamic parameters such as plasma area under the curve. The analysis employed various linear models, with a particular emphasis on linear mixed-effect models (LMEMs) that demonstrated exceptional accuracy. The model was validated via the preparation and administration of two distinct NP formulations via the intranasal and intravenous routes. Among the various modeling approaches, LMEMs exhibited superior performance in capturing underlying patterns. Factors such as the release rate and molecular weight had a negative impact on brain targeting. The model also suggests a slightly positive impact on brain targeting when the drug is a P-glycoprotein substrate.