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Category: genetics

Advancements in organoid models emulating metastatic niches

Metastatic niche in organoid models.

The mortality rate of cancer patients remains high, mainly due to the lack of metastasis-tailored treatments, highlighting the need for alternative experimental approaches that capture metastatic development in a human context.

Human-induced pluripotent stem cell derived organoids cocultured with cancer cells (‘chimeroids’) have the potential to emulate aspects of colonized organ specific microenvironments and offer an alternative platform for target identification and drug discovery, as these models are amenable to scalable genetic and chemical perturbation screens.

Conceptually, organoid models have progressed from epithelial-only organoids to multilineage, niche enriched systems incorporating stromal, vascular, and tissue-resident immune components, thereby bringing in vitro models closer to organ-specific metastatic microenvironments.

Yet no single organoid model fully recapitulates the entire complexity of an organ in vivo; thus, model selection must be driven by the specific scientific question, ensuring that the relevant stage of metastatic development and organ microenvironment are appropriately represented. ScienceMission sciencenewshighlights https://sciencemission.com/organoid-models-emulating-metastatic-niches

Metastases cause most cancer-related deaths, underscoring the need for therapies targeting metastatic stages, including the tumor microenvironment. Yet translating biological insights into treatments remains difficult. Preclinical metastasis research largely relies on rodent models, which have species-specific limitations and are incompatible with large-scale perturbation screens in a human context. Human organoids aim to emulate organ microenvironments in vitro and, when cocultured with cancer cells, can provide complementary models. These ‘chimeroids’ may enable scalable studies of cancer–microenvironment interactions and support genetic and pharmacological screens to discover new targets, offering insights into the final, often lethal step of metastasis—tissue colonization.

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A new era in childhood obesity

Childhood obesity!

Obesity associated with the melanocortin system can be diagnosed in childhood, including both monogenic and syndromic forms.

Genetic obesity is characterized by early onset and extreme hyperphagia, although there is no precise definition for these features.

Numerous polymalformative syndromes include obesity among their main phenotypic traits. Among these are ciliopathies, in which alterations in the neuronal ciliary system can disrupt hypothalamic proopiomelanocortin neuron signaling, helping to explain the hyperphagia and obesity frequently observed in some of these disorders.

Pharmacological treatment of patients with impairment of the leptin– melanocortin pathway can be classified into specific and nonspecific treatments.

The use of these therapies is expanding to new indications, and additional treatments are under clinical investigation for both monogenic and polygenic obesity sciencenewshighlights ScienceMission https://sciencemission.com/childhood-obesity-19506

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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.

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.

Seed banks may complicate gene drives aimed at controlling weeds

Gene drives—a genetic engineering approach that quickly spreads specific genetic changes throughout a population, whether to kill it off or add a new trait—may have potential for controlling weeds. But so far, gene drives have primarily been studied in mosquitoes, and have yet to be deployed in the real world.

In a first-of-its-kind study, researchers modeled how a gene drive would proceed in plants. Their simulations suggest that a gene drive’s success may hinge on seed banks—underground reservoirs of seeds that can germinate years or even decades later. Without proper consideration, they found, these stored seeds can slow down or even doom the gene drive, because they continually reintroduce plants without the gene drive into the population.

Modeling studies like this one can help scientists design successful gene drives in plants and discover and mitigate potential problems before deployment in the wild, the researchers said.

Abstract: Genetic analysis of neurodegenerative diseases:

As part of the JCI’s Review Series on Neurodegeneration, Sonja W. Scholz and colleagues highlight key genomic technologies advancing diagnosis and research in neurodegeneration.

1Neurodegenerative Diseases Research Section, National Institute of Neurological Disorders and Stroke;

2Neurogenetics Branch, National Institute of Neurological Disorders and Stroke; and.

3Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA.

Zebrafish reveal new insights into the biology of autism

In recent decades, the zebrafish has become one of the most valuable model organisms in scientific research. For a variety of reasons, including their genetic similarities to humans, these tiny tropical fish have helped researchers unlock secrets to diseases ranging from muscular dystrophy to melanoma. Now, Yale researchers are hoping the zebrafish will do the same for autism spectrum disorder.

In a new study, a research team generated a database of 520 U.S. Food and Drug Administration (FDA)-approved drugs and their effects on basic larval zebrafish behaviors and then used the database to identify drug candidates that reverse disrupted behaviors in zebrafish carrying mutations in autism risk genes.

These drug candidates, the researchers say, might represent targets for people carrying mutations in specific autism risk genes.

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