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Category: genetics

C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA: RNA hybrid G-quadruplexes

Transcriptional dysregulation hexanucleotide repeats in ALS

Repeat hexanucleotide RNAs in C9orf72 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia disease pathogenesis but the mechanisms of action remain incompletely understood.

The researchers demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form DNA: RNA hybrid G-quadruplexes (HQs) structures with DNA.

These structures obstruct RNA polymerase II and transcription factors, repress gene expression, and heighten neuronal vulnerability, providing mechanistic insights into neurodegeneration in ALS and FTD. sciencenewshighlights ScienceMission https://sciencemission.com/hexanucleotide-repeat

Liu et al. demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form HQ structures with DNA. These structures obstruct key transcription machinery, repress gene expression, and heighten neuronal vulnerability, providing mechanistic insights into neurodegeneration in ALS and FTD.

Interactive Zebrafish Embryo Single-Cell Atlas

A developmental atlas for genes and cells.

The interplay between genes and cells during the development of a fertilized egg into an embryo is highly complex. Previous methods captured gene activity only in 2D slices, making whole-embryo visualization impossible and offering limited spatial detail, often missing subcellular patterns.

The new method now enables the research team to visualize the activities of thousands of genes throughout the entire embryo and link them to cell maturation and movement. The result is a comprehensive atlas of early development, along with new insights into how genes and cells shape the growing embryo. The study was published in Science.

The team developed a new imaging technology called weMERFISH. It enables the direct measurement of the activity of nearly 500 genes in entire tissues with subcellular resolution.

From these measurements, the researchers created an atlas of early embryonic development. “By combining previous single-cell data with our gene activity measurements, we were able to calculate spatial patterns of thousands of genes and the activity of around 300,000 potential regulatory regions,” says the author. The data are freely accessible through the web platform MERFISHEYES (http://schier.merfisheyes.com). “The atlas is intended as a resource for developmental biologists around the world.”

With the help of the atlas, the researchers were also able to clarify how clear boundaries between different tissues form, for example between muscle and backbone tissue. They discovered a zone of cells in which the activity of many genes changes dramatically and differs from one side to the other.

A comparison of early and later stages showed that these genes are initially active on both sides but later only on one. And there are hardly any cells that cross this boundary. “These boundaries do not arise because cells are intermingled and then sort, but mainly because cells change their genetic program,” says the author.

Continue reading “Interactive Zebrafish Embryo Single-Cell Atlas” | >

Cell-type specific TDP-43 pathology in the motor cortex

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions.

Lp(a) Explained: Genetics, Risk, and What You Can Actually Do

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The Genetics of Living Longer: Study Challenges Decades of Aging Research

What determines how long people live, and how much of their lifespan is influenced by genetics?

For many years, scientists believed the genetic contribution to human lifespan was relatively modest compared with other biological traits. Earlier estimates placed the heritability of lifespan at around 20 to 25 percent, and some more recent large studies suggested it might be even lower, in some cases below 10 percent.

A new study from the Weizmann Institute of Science now challenges that view. The research, published in the journal Science, reports that genetic differences may account for roughly half of the variation in human lifespan. This estimate is more than double many previous calculations. The work was led by Ben Shenhar in the laboratory of Prof. Uri Alon of the Weizmann Institute’s Molecular Cell Biology Department.

New DNA tools outperform traditional methods for detecting genetic risk in wildlife

Wildlife populations that become small and isolated, often due to habitat loss, inevitably experience inbreeding which can lead to the loss of fitness and eventual extinction. One solution is to perform a genetic rescue: a management intervention where new blood is brought in by introducing outsiders to a population to reduce inbreeding and restore diversity. But how do researchers know the inbreeding problem has been solved?

A new long-term study from Western, led by biology professor and chair David Coltman, shows DNA-based tools detected changes in inbreeding more accurately than traditional pedigree methods in a wild population of bighorn sheep that was recently genetically rescued. The study was published in the journal Evolutionary Applications.

Pedigree approaches estimate genetic health from family history, whereas genomic approaches directly analyze DNA.

Oligodendrocyte molecular perturbations associated with tau in Alzheimer’s

The findings suggest that in AD, part of what happens in the brain may involve changes in DNA tagging that affect the function of oligodendrocytes, particularly in relation to the buildup of the toxic protein tau.

Oligodendrocytes are the brain cells that make myelin, the insulation that helps nerve cells communicate. Scientists have theorized that disrupting neuron communication contributes to symptoms for people with AD. Researchers in this study found that nearly all significant methylation changes — small chemical tags added to DNA that help control when genes are turned on or off — were linked to the tau protein. This supports the idea that this protein plays a key role in brain cell changes tied to AD.

“Our team has previously shown that oligodendrocytes are affected in Alzheimer’s and another tau-related disease, progressive supranuclear palsy (PSP),” says the author. “These new results further highlight that problems in oligodendrocytes and myelin are central to AD. They also point to specific molecular pathways, particularly epigenetic changes, that could be targeted in future therapies.”

The study results identified new genes that may play a role in AD, including one called LDB3, and confirmed many findings across multiple independent datasets, showing its reliability. The identification of specific genes provides potential targets for future research — for example, scientists might investigate whether interventions that reverse methylation or support oligodendrocyte health can slow or modify disease progression for patients with AD. ScienceMission sciencenewshighlights.

In a study published in Nature Communications, the researchers have identified specific DNA-level changes in the brains of people with Alzheimer’s disease (AD). Using advanced biological analysis, the team mapped alterations in the brain’s regulatory landscape that may help explain why Alzheimer’s presents and progresses differently from person to person. The findings could also open new avenues for understanding other neurodegenerative diseases.

Alzheimer’s disease is the most common cause of dementia. Biologically, the disease begins with the formation of protein deposits, known as amyloid plaques, and neurofibrillary tangles in the brain. This causes brain cells to die over time and the brain to shrink. About 6.9 million people in the U.S. age 65 and older live with Alzheimer’s disease. There is no cure, and in advanced stages, complications can result in a significant decline in quality of life and death.

Continue reading “Oligodendrocyte molecular perturbations associated with tau in Alzheimer’s” | >

Enhancer dynamics and cellular architecture in the human spinal cord

Human spinal cord enhancer dynamics and cellular architecture.

The researchers present an innovative framework redefining human spinal cord cellular diversity through epigenetic configuration and spatial organization.

They identify unseen enhancer classes that define both stable cell-type identity and transitions between cells undergoing differentiation.

The authors also identify gene regulatory networks in glial cells that reorganize along the rostrocaudal axis, demonstrating anatomical differences in gene regulation.

The researchers demonstrate spatial organization of cells into distinct cellular networks and address the functional significance of this observation in the context of paracrine signaling. sciencenewshighlights ScienceMission https://sciencemission.com/Enhancer-dynamics

Kandror et al. present an innovative framework redefining human spinal cord cellular diversity through epigenetic configuration and spatial organization. They identify unseen enhancer classes, show cell-type-specific reconfiguration of gene regulatory networks along the rostrocaudal axis, and uncover cellular networks mediated by discrete paracrine signaling, challenging conventional definitions of cellular state.

Continue reading “Enhancer dynamics and cellular architecture in the human spinal cord” | >

AI finally tests a century old theory about how cancer begins

Cancer often begins when the genetic instructions that guide our cells become scrambled, allowing cells to grow uncontrollably. Now, scientists at EMBL have developed an AI-powered system called MAGIC that can automatically spot and tag cells showing early signs of chromosomal trouble—tiny DNA-filled structures known as micronuclei that are linked to future cancer development.

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