A new study raises important questions about widely used NAD+ supplements, suggesting that compounds often taken to boost energy and support healthy aging may have unintended consequences in cancer treatment.
Category: biotech/medical
New genetic toolkit enables genome-wide analysis
Researchers at Cornell University have developed a powerful new genetic toolkit that allows scientists to study how genes function at the level of individual cells, an advance that could accelerate discoveries in development, neuroscience and disease.
The system builds on MAGIC (Mosaic Analysis by gRNA-Induced Crossing-over), a method originally created by the labs of Chun Han, associate professor in the Department of Molecular Biology and Genetics in the College of Agriculture and Life Sciences (CALS) and the Weill Institute for Cell and Molecular Biology. MAGIC uses CRISPR gene editing to generate individual mutant cells within otherwise normal tissue, enabling precise comparisons within a living organism.
In the new study, graduate researcher Yifan Shen expanded the approach into a genome-wide toolkit for Drosophila melanogaster, creating resources that work across all chromosomes and allow researchers to study genes that were previously difficult, or impossible, to analyze at single-cell resolution.
Tomatidine is a senotherapeutic compound that improves cognitive function and reduces cellular senescence in aged mice
Cellular senescence drives aging and age-related dysfunction across multiple tissues, including the brain. Through a high-content, senescent cell-based phenotypic screen of a small panel of natural products, we identified tomatidine, an aglycone of tomatine found in tomatoes, as a previously unrecognized senotherapeutic agent. In senescent human brain microvascular endothelial cells and fibroblasts, tomatidine selectively suppressed SASP expression without affecting p16Ink4a or p21Cip1 levels consistent with a senomorphic effect. In aged mice, tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by reduced senescence markers (p16 Ink4a, p21 Cip1, and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, along with decreased neuroinflammation and microglial activation. Tomatidine also diminished brain endothelial cell senescence while enhancing tight junction protein expression, suggesting preserved blood–brain barrier integrity. Together, these findings identify tomatidine as a promising senescence-targeting compound with beneficial effects in aged mice and support its further evaluation in mechanistic and translational studies.
ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and —independent mechanisms
We report that the RNA-editing enzyme ADAR1 downregulates nuclear-and mitochondria-encoded double-stranded RNAs (dsRNAs) to maintain immune homeostasis. ADAR1 employs RNA-editing-dependent and-independent mechanisms to keep dsRNA levels low in cells. Notably, upon ADAR1 loss, mitochondrial dsRNA levels increase and can cause enhanced inflammation upon mitochondrial stress.
Endogenous aldehydes: A driver of clonal hematopoiesis from within?
Detoxification of endogenous aldehydes is critical for preserving genomic integrity in hematopoietic stem cells. In this issue, Kamimae-Lanning et al. show that excess formaldehyde can drive clonal hematopoiesis through attrition of blood-forming progenitors, accelerating neutral drift in the absence of known genetic drivers of positive selection.
MICrONS Explorer: A virtual observatory of the cortex
The Machine Intelligence from Cortical Networks (MICrONS) program seeks to revolutionize machine learning by reverse-engineering the algorithms of the brain. It is an ambitious program to map the function and connectivity of cortical circuits, using high throughput imaging technologies, with the goal of providing insights into the computational principles that underlie cortical function in order to advance the next generation of machine learning algorithms.
This website serves as a data portal to release connectivity and functional imaging data collected by a consortium of laboratories led by groups at the Allen Institute for Brain Science, Princeton University, and Baylor College of Medicine, with support from a broad array of teams, coordinated and funded by the IARPA MICrONS program. These data include large scale electron microscopy based reconstructions of cortical circuitry from mouse visual cortex, with corresponding functional imaging data from those same neurons.
Have a Scientific Request? Check out the Virtual Observatory of the Cortex (VORTEX) project, a BRAIN Initiative funded program to bring the MICrONS dataset to the research community. Access proofreading resources to answer your scientific questions.
Reconstructing tumor tissues in 3D: From organoids to bioengineered niches
Tumor tissue engineering has opened new avenues for cancer research. With an emphasis on gastrointestinal malignancies, we summarize capabilities and limitations of patient-derived and engineered organoid models. We then discuss how innovations in biomaterial design, biofabrication, microfluidics, benchmarking, and AI converge to better emulate tumor tissues and advance translational modeling.
Stress tested, testing stress: Novel organoid models how the adrenal gland develops
Sitting above each kidney are two small endocrine glands about the size of walnuts. These are the adrenal glands, responsible for producing hormones that help control some of the body’s most critical functions. Among these hormones, cortisol is particularly critical for survival. Often referred to as the “stress hormone,” it helps the body adapt to a wide range of challenges—both emotional and physical, such as trauma or infection—by regulating overall metabolism. Despite its central role in stress and endocrine biology, how the adrenal gland is built and how it functions remains poorly understood.
Now, researchers led by Kotaro Sasaki and Michinori Mayama of the School of Veterinary Medicine have developed a lab-grown organoid system that recapitulates the complex tissue structure, development, and function of the developing human adrenal cortex—the outer layer of the adrenal gland—providing a powerful platform to study its biology. These results, published in Cell Stem Cell, help establish a foundation for regenerative therapies targeting adrenal diseases.
“The adrenal cortex is a major endocrine organ and central to our stress response,” says Sasaki, the Richard King Mellon Associate Professor of Biomedical Sciences. “Despite its importance, adrenal biology has lagged behind that of other organs. Our goal was to create a mini adrenal gland in a dish to better understand how the human adrenal forms and begins to function.”